Tarmander

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So, pyroglutamic acid actually has several names including 5-oxo-proline / 5-keto-proline. In other words, it is proline with an extra oxygen atom and Peat has written about the beneficial effects of proline along with those of glycine. I think the choice of name "pyroglutamic" is unfortunate as it confuses people. In reality, L-PGA seems to act like an antagonist to glutamate and seems to increase GABA signalling (where it is needed). The Wiki link in regards 5-HT2B antagonism mentions that. Another glutamate analog is the amino acid theanine and it is also known to antagonize glutamate and promote GABA.
Theanine - Wikipedia
Inosine may raise uric acid but human studies showed that only chronic daily doses of 3g or more led to elevations of uric acid beyond the acceptable range.
The only side effects I had when testing this was overstimulation and trouble sleeping, which is a known side effect of ATP administered through infusion. Hence, the design of the product to be used every other day instead of daily like the other products we have.
Thank you!
 

haidut

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Haidut, I'm wondering if, given the neuroprotective properties of this supplement, it might be of help systemically to those with Parkinson's, particularly if taken with Oxidal/MB?

Can't speak about specific conditions but the combination of L-PGA + B6 does seem to raise dopamine quite a bit, so in theory should help dopamine deficiency states. That is why it is used for ADHD, which is also a dopamien deficiency state.
 

haidut

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so this is anti-hang-over product you were mentioning as well or will you release another product specific for that purpose??

Yes, the combination of L-PGA and B6 is the antihangover product I had in mind. Originally, I thought of adding succinic acid to it and releasing as a separate AlcoBan product but then I realized the effects are due to raising ATP and since I had an ATP product in the works I thought it would be best to combine them both because of synergistic effects and to not have people spend money on two separate supplements that actually work best together.
 

haidut

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I gotta ask...is this legal?

I’m assuming this isn’t FDA approved, in which case is it enough to just declare ‘for R&D purposes’ in the title, even though it’s clear and obvious from the accompanying marketing language that it is being recomended, marketed and distributed for general use as a supplement by whoever orders it? Is it really that easy to bypass the regulations?

I’m not questioning the effectiveness or safety of this thing, just the legality of making it and selling it.

Why wouldn't it be legal? None of the ingredients is a controlled substance and how people use it is their business. We are just not advertising it for human consumption. As you probably know, you can buy liquid aromatase inhibitors like letrozole / anastrozole, SARMs, SERMs (tamoxifen, clomiphene), etc from various US-based vendors and they market their products for "R&D purposes only". Ultimately, it comes down to safety and potential for abuse. In this product, everything is substance that exists in the organism naturally or in the diet, and none of the ingredients is a controlled substance like those SARM/SERM, AI or designers steroids which also available legally.
 

haidut

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According to a study perforemed by a major skincare and chemical-actives enterprise, at least in aged skin cells not ATP in itself is the major probelem, but mitochondrial Creatinkinase (mtCK).
I'll find the study meanwhil I'll losely translate the major bit:

In Skin cells of aged probands, function of mtCK is diminished and malfunctioning leading to less stimulation of mitochondrial OXPHOS,
Phospho-creatine pool maintenance is slowed down and local supply of PCr is insufficinet.
Cytosolic Creatinkinase is no longer bal to maintain and stabilize ATP-Concentration in that cells. Higher ADP-concentration leads to glycolysis to maintain ATP-concetration and functioning of local ATPasen.

The study further sais that ATP needs Creatinkinases to "leave" the mitochondria and be recycled from the cytosols?
Anybody ever thought about that angke.

The said PhD thesis is in german only, but the main synopsis is that things like Q10 and so forth are not significantly different in aging skin but for the insufficnnet couplin of Creatinkinase to mito ATP-synthesis - leading to many detrimental consequences in skin energy metabolism. (Not surprisingly, old skin cells use Glycolysis for ATP as said, wih a lot of lactate then damaging the skin)

Is this not of importance when supplementing ATP in therory? How to increase mtCK? Creatine? In the Diss at least they provide evidence for enrichng skincreams with Creatine

I suppose adding creatine could help improve ATP, but in my experience succinic acid is a much better and more direct precursor. Creatine is more of a buffer that can be used to provide emergency ATP source. On the other hand, succinic acid HAS to be metabolized into ATP as that is the ultimate destination of all food we eat and that food (after a few steps) always goes through the succinic acid step.
 

Wagner83

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Great catch! The correct dose is 40 drops, so the label is right. I updated the original thread description.
Oxidal complements this greatly! So, thanks so much for bringing this up. In fact, I will update the original thread and mention this.
The reason for synergy is that methylene blue (MB) helps the ETC function better if there is block anywhere in the stages I - IV. So, if somebody takes succinic acid and their ETC is not functioning well for some reason then there won't be as much boost as the ETC was operating well and the electrons from succinic acid were able to flow to O2 at the end. MB proides this alternative electron acceptor, which has been shown to restor electron flow along the ETC in case of damage. And in case of well working ETC it can speed it up even more.
Bypassing the compromised mitochondrial electron transport with methylene blue alleviates efavirenz/isoniazid-induced oxidant stress and mitochondria-mediated cell death in mouse hepatocytes - ScienceDirect
Mitochondrial pharmacology: Electron transport chain bypass as strategies to treat mitochondrial dysfunction
Alternative Mitochondrial Electron Transfer as a Novel Strategy for Neuroprotection

Another chemical that can speed up the process of succinic acid oxidation is riboflavin (e.g. Energin) as it is the precursor of FAD and FAD is the cofactor for succinic dehydrogenase which metabolizes succinic acid. In fact, riboflavin is present in the drug cytoflavin I mentioned above, for that very reason. The active form R5P would work even better. However, riboflavin/R5P/FAD will not help in case of ETC damage/malfunction. It would only speed up the Krebs cycle side of the reaction.
Ok cool! Some people don't tolerate MB, could you briefly compare the difference in effects betweenMB and this new supplement or even inosine?
By the way I've been wondering if exercise lowers BP (you were a former athlete and love your MB) then perhaps exercise would be a nice supplement to a MB regimen ?
 

Koveras

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Also ,other then Inosine, will any of the ingredients raise Uric Acid? I don't think so, but want to make sure.

Inosine may raise uric acid but human studies showed that only chronic daily doses of 3g or more led to elevations of uric acid beyond the acceptable range.

Oral ATP raises uric acid as well, although the acute doses were high

Adenosine 5'-triphosphate (ATP) supplements are not orally bioavailable: a randomized, placebo-controlled cross-over trial in healthy humans.

"A single dose of orally administered ATP is not bioavailable, and this may explain why several studies did not find ergogenic effects of oral ATP supplementation. On the other hand, increases in uric acid after release of ATP in the proximal part of the small intestine suggest that ATP or one of its metabolites is absorbed and metabolized. Uric acid itself may have ergogenic effects, but this needs further study. Also, more studies are needed to determine whether chronic administration of ATP will enhance its oral bioavailability."​

Oral bioavailability of ATP after prolonged administration.

"ATP supplementation for 4 weeks did not lead to changes in blood or plasma ATP concentrations. Of all ATP metabolites, only plasma uric acid levels increased significantly after the administration of 5000 mg of ATP. Prolonged administration of ATP was safe as evidenced from liver and kidney parameters. We conclude that oral administration of ATP only resulted in increased uric acid concentrations."
Screen Shot 2018-02-10 at 7.55.22 AM.png Screen Shot 2018-02-10 at 7.55.57 AM.png
 

mirc12354

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Yes, the combination of L-PGA and B6 is the antihangover product I had in mind. Originally, I thought of adding succinic acid to it and releasing as a separate AlcoBan product but then I realized the effects are due to raising ATP and since I had an ATP product in the works I thought it would be best to combine them both because of synergistic effects and to not have people spend money on two separate supplements that actually work best together.
how much would you take in order to prevent hangover?before or after heavy night out?
 

Koveras

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I suppose adding creatine could help improve ATP, but in my experience succinic acid is a much better and more direct precursor. Creatine is more of a buffer that can be used to provide emergency ATP source. On the other hand, succinic acid HAS to be metabolized into ATP as that is the ultimate destination of all food we eat and that food (after a few steps) always goes through the succinic acid step.

I've seen that even a mild dietary phosphorous deficiency can impair cell ATP levels. Creatine will also increase phosphate requirements and uptake - potentially a mechanism for creatine induced muscle cramps if that mild dietary phosphate deficiency is present and/or if there is insulin resistance. Important to consider, especially for athletes, considering the general emphasis on reducing phosphate intake here. ATP in this product comes with its own phosphate, but I assume ramping up ETC or utilizing the purine salvage pathways could increase phosphate requirements further.
 

Tarmander

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Oral ATP raises uric acid as well, although the acute doses were high

Adenosine 5'-triphosphate (ATP) supplements are not orally bioavailable: a randomized, placebo-controlled cross-over trial in healthy humans.

"A single dose of orally administered ATP is not bioavailable, and this may explain why several studies did not find ergogenic effects of oral ATP supplementation. On the other hand, increases in uric acid after release of ATP in the proximal part of the small intestine suggest that ATP or one of its metabolites is absorbed and metabolized. Uric acid itself may have ergogenic effects, but this needs further study. Also, more studies are needed to determine whether chronic administration of ATP will enhance its oral bioavailability."​

Oral bioavailability of ATP after prolonged administration.

"ATP supplementation for 4 weeks did not lead to changes in blood or plasma ATP concentrations. Of all ATP metabolites, only plasma uric acid levels increased significantly after the administration of 5000 mg of ATP. Prolonged administration of ATP was safe as evidenced from liver and kidney parameters. We conclude that oral administration of ATP only resulted in increased uric acid concentrations."
View attachment 8337 View attachment 8338
Thank you!
 

GAF

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I notice that distilled water is the only additional ingredient so does that mean this product is designed for oral intake. There appear to be no topical absorption enhancers.

Also, it appears to me that this product does not have to be limited to the lab chemical section. Why not also include it in the supplement section, since
you can get all these ingredients on Amazon if you wanted

Or, technically, should it only be in the supplement section?
 

haidut

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Ok cool! Some people don't tolerate MB, could you briefly compare the difference in effects betweenMB and this new supplement or even inosine?
By the way I've been wondering if exercise lowers BP (you were a former athlete and love your MB) then perhaps exercise would be a nice supplement to a MB regimen ?

Well, MB is just an electron carrier, an oxidizing agent. So, it is the spark that helps burn the fuel. However, if the Krebs cycle is not working well and not enough electrons reach the ETC then MB probably won't do much for ATP even tough it has other benefits such as lowering inflammation (as per my other recent post). Succinic acid and inosine are kind of like pre-formed ATP precursors, which have been shown to raise ATP in humans and animals, and MB can make that process even more efficient. So, Oxidal and Energin would be the spark and Cardenosine the fuel in my analogy.
Exercise seems to lower BP due to keeping blood vessels flexible, and it also lowers heart rate. If MB raises BP then I would try some taurine, and/or vitamin K/D as it could be an issue with vascular calcification and those have been shown to reverse it. Exercise may help too, so I would use whatever works best for the specific person.
 

haidut

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Oral ATP raises uric acid as well, although the acute doses were high

Adenosine 5'-triphosphate (ATP) supplements are not orally bioavailable: a randomized, placebo-controlled cross-over trial in healthy humans.

"A single dose of orally administered ATP is not bioavailable, and this may explain why several studies did not find ergogenic effects of oral ATP supplementation. On the other hand, increases in uric acid after release of ATP in the proximal part of the small intestine suggest that ATP or one of its metabolites is absorbed and metabolized. Uric acid itself may have ergogenic effects, but this needs further study. Also, more studies are needed to determine whether chronic administration of ATP will enhance its oral bioavailability."​

Oral bioavailability of ATP after prolonged administration.

"ATP supplementation for 4 weeks did not lead to changes in blood or plasma ATP concentrations. Of all ATP metabolites, only plasma uric acid levels increased significantly after the administration of 5000 mg of ATP. Prolonged administration of ATP was safe as evidenced from liver and kidney parameters. We conclude that oral administration of ATP only resulted in increased uric acid concentrations."
View attachment 8337 View attachment 8338

The human studies in the ATP section of the thread show positive effects from oral ATP administration. Yes, most of it breaks down into adenosine and phosphate but the purine salvage pathway seems to be pretty efficient in regenerating that ATP using the resulting adenosine. In addition, rodent studies show that about 10% of orally administered ATP enters circulation unchanged (i.e. without breakdown). Furthermore, one of the rodent studies, also in that ATP section, shows that chronic feeding of ATP orally made the rodents really efficient at converting food into ATP, so the positive effects may be more related to how exogenous ATP changes the physiology than its direct contribution as a purine.
So, exogenous ATP definitely has effects and I hoping that further human studies will elucidate the mechanism.
 

haidut

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how much would you take in order to prevent hangover?before or after heavy night out?

I would use a single dose (40 drops) about 1 hour before drinking. I don't think a second dose is needed. Higher doses, equivalent to 2 servings (80 drops) daily have been used to treat cirrhosis and other liver diseases.
 

haidut

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How is ribose metabolized?

Ribose actually shares a common pathway with inosine for re-generating ATP. Ribose gets converted into ribose-5-phosphate, then this ribose-5-P gets converted into phosphoribosyl pyrophosphate (PRPP), then PRPP gets converted into phosphoribosylamine, which then gets converted into inosine-5-monophosphate (IMP). Inosine also replenishes ATP through conversion into IMP. But inosine already contains ribose within its structure, so I don't think there is need to add even more ribose as a separate ingredient in this product.
 

haidut

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I've seen that even a mild dietary phosphorous deficiency can impair cell ATP levels. Creatine will also increase phosphate requirements and uptake - potentially a mechanism for creatine induced muscle cramps if that mild dietary phosphate deficiency is present and/or if there is insulin resistance. Important to consider, especially for athletes, considering the general emphasis on reducing phosphate intake here. ATP in this product comes with its own phosphate, but I assume ramping up ETC or utilizing the purine salvage pathways could increase phosphate requirements further.

True, good points. I may actually change the inosine to inosine-5-monophosphate (IMP) since that way it will also have its own phosphate supply, leaving only succinic acid competing for phosphate groups. IMP is harder to source, but I will see what can be done. It is more water-soluble than inosine so I may be able to dissolve more per dose and make this even more effective.
 

haidut

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I notice that distilled water is the only additional ingredient so does that mean this product is designed for oral intake. There appear to be no topical absorption enhancers.

Also, it appears to me that this product does not have to be limited to the lab chemical section. Why not also include it in the supplement section, since


Or, technically, should it only be in the supplement section?

Succinic acid is a transdermal enhancer and so is pyroglutamic acid.
[Oleyl pyroglutamate for use as transdermal enhancer and its enhancing mechanism]. - PubMed - NCBI
http://www.pharmtech.tu-bs.de/files/muegoy/JFokuhlJena0910.pdf

We may move it to the supplement section. I am waiting on our lawyer to opine on the matter.
 
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