1. Cocoa Butter - Organic & Fair Trade Certified
    CLICK HERE!
    Dismiss Notice
  2. **NEW** BL11 - Orange, Red & Infrared Therapy Body Light
    CLICK HERE!
    Dismiss Notice
  3. Charcoal Soap - For Deep Cleansing
    CLICK HERE!
    Dismiss Notice
  4. Orange & Red Light Therapy Device - LGS1
    CLICK HERE!
    Dismiss Notice
  5. Organic Cocoa Powder
    CLICK HERE!
    Dismiss Notice
  6. Metabasoap - Handcrafted Soap
    CLICK HERE!
    Dismiss Notice
  7. Cascara Sagrada Powder From Farmalabor In Italy
    CLICK HERE!
    Dismiss Notice
  8. **NEW Mini Body Light** MBL1 - Orange & Red Light Therapy Mini Body Light
    CLICK HERE!
    Dismiss Notice

Pyrucet - Liquid (ethyl) Pyruvate/Aceatoacetate Mix

Discussion in 'IdeaLabs' started by haidut, Jan 30, 2019.

  1. truegrit

    truegrit Member

    Joined:
    Oct 6, 2017
    Messages:
    11
    Gender:
    Male
    I too ordered Pyrucet the day it was available. 20 drops orally seems to palpably increase hunger so definitely make sure you're in a thoroughly fed state or give with sugar to offset. Other than that, nothing profound to report yet. I am primarily taking for exercise performance as an analog to Mildronate as discussed a few times elsewhere, so that makes me a minority use case. I am particularly interested to see if there is any synergy with Cardenosine as well.
     
  2. tallglass13

    tallglass13 Member

    Joined:
    Dec 29, 2015
    Messages:
    288
    Gender:
    Male
    Occupation:
    Registered Nurse
    @haidut, what would happen if someone was doing Keto or low carb diet, and used Pyrucet?
     
  3. GAF

    GAF Member

    Joined:
    Dec 28, 2014
    Messages:
    535
    Gender:
    Male
    Occupation:
    CPA
    Location:
    Dallas Texas
    It's 5:31 pm in Texas. In my 62 yr old body, 20 drops internally provided major energy and focus boost. As noted above, the need for fuel increased as one would expect when your energy level is doubled or tripled. I think I will keep doing the 20 drops internally right when I wake up in the morning for a week and see how long I can keep this power surge going. I need the extra energy to get all my CPA work done for sure, so if the surge keeps going, it will be a great blessing to my bank account. It's no problem for me to snack along the way all day.

    GF had 10 drops on arm and received a boost but not as dramatic as my boost and She also needed snacks to keep from sinking. I think I will adjust her daily dose to 3 drops 3 times a day - topical - and keep her fed along the way. She has a lot better normal energy than I do so I don't think she would really like a rocket boost.

    There seems to be a myriad of ways to use this stuff. Getting extra energy on demand with the 20 drop bomb can come in handy. I hope some peoples will experiment with something like a topical drop or two per hour to see if they can keep their motor running at high speed hour after hour.

    Very very interesting product with lots of options for people with different needs and requirements.

    I will probably go dancing tonight and see how much extra quickness and speed I have 9 hours after a 20 drop shot. Say a prayer for my GF/dance partner...
     
  4. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,169
    Gender:
    Male
    Location:
    USA / Europe
    Thanks for the feedback. Please do share your experience when you combine with Cardenosine.
     
  5. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,169
    Gender:
    Male
    Location:
    USA / Europe
    I think both of the chemicals trigger insulin release and may interrupt the ketosis. I don't think it should be used by people in ketosis, this product tries to do the very opposite of what ketosis does.
     
  6. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,169
    Gender:
    Male
    Location:
    USA / Europe
    I think the effects of the ethylated esters of the chemicals in Pyrucet are not (mainly) due to their usage as fuel precursors but rather because they activate PDH. Maybe higher doses could have the circumventing effect you mention but at the doses in Pyrucet the main effects should be simply activation of PDH and then if glucose is available it should flow through PDH and form acetyl-CoA.
     
  7. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,169
    Gender:
    Male
    Location:
    USA / Europe
    Thanks.
    @mirc12354
     
  8. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,169
    Gender:
    Male
    Location:
    USA / Europe
    That I don't know, but I think in that case the ratio would the least of these people's worry. If the toxicity is severe enough then chelation needs to be considered or organ damage can easily occur.
     
  9. High_Prob

    High_Prob Member

    Joined:
    Mar 23, 2016
    Messages:
    199
    Gender:
    Male
    @haidut Would taking Niacin/Niacinamide at the same time as Pyrucet be counterproductive (as far as the interaction with acetoacetate)?


    Cancer Addiction To Fat Confirmed; Niacinamide As Possible Treatment

    "This is the latest of a number of studies over the last year or so that point the finger at fat (and not sugar) as the primary factor in tumor growth. I posted a few studies in the past showing that tumor cells are highly dependent on fat for growth and proliferation, and a number of hypolipidemic agents like orlistat or even niacinamide can help curb, or even completely reverse tumor growth. In combination with a fatty acid oxidation inhibitor like Mildronate, the effect will probably be even more potent. And adding a fatty acid synthase (FAS) inhibitor like vitamin D or aspirin on top of that can create a well-rounded cancer treatment for most cancer types.
    Cancer Cells Addicted To Fat And Use Fat Oxidation For Survival
    Achilles Heel Of Cancer Found - Its Addiction To Fat
    Niacinamide Can Cure Liver (and Maybe Pancreatic) Cancer
    This study adds to the evidence for the role dietary fat and diet-induced ketogenesis in the progression of tumors. Interestingly, just like the study on liver and pancreatic cancer I posted just a few days ago, administering niacin was very effective as an anti-cancer agent. Ray has written quite a bit about the tendency of cancer patients to fall into ketosis, and this study confirms his statements. Niacin lowered the levels of acetoacetate (a biomarker of ketosis) and greatly inhibited tumor growth. The HED of nacin was about 15mg/kg and treatment was for 3.5 weeks. For the record, niacinamide is even more effective than niacin in interrupting ketosis, so using niacinamide at that dose would probably achieve even better results. Interestingly, this same dose of about 1.5g niacinamide daily was successfully used to improve type II diabetes in human trials and in animal trials it basically reversed the condition. I doubt these findings are just a coincidence given the link between lipolysis, ketogenesis, diabetes, and cancer.
    As the study says, while the study only focused on one type of cancer (and its mutation), the morale of the story is that high-fat, low-carb diets are probably not good for cancer patients. Fasting also accelerated tumor growth, due to the increase in ketogenesis. Finally, the ketone acetoacetone not only served as fuel for the tumors but also had genomic/receptor effects, which also promoted tumor growth.

    Melanoma mutation likes fat for fuel: Diet can modulate growth-spurring effect in mice
    "...Cancer cells love glucose, so a high-fat, low-carb diet should starve them, right? Not cancers driven by a notorious melanoma mutation. Research in mice suggests that cancers with BRAF V600E will grow faster in response to a high-fat 'ketogenic' diet. In addition, lipid-lowering agents such as statins curb these cancers' growth, even in the context of a more normal diet."

    "...Most cancer cells display enhanced glucose uptake, a phenomenon known as the Warburg effect. A low-carb diet has been tried as a clinical countermeasure in a limited way, mainly in brain cancer. In contrast, a possible implication of the Winship researchers' results is that people fighting a cancer with a BRAF V600E mutation should avoid low-carb diets."

    "...One of the alternative energy sources produced by ketogenesis is acetoacetate. Within cancer cells with the V600E mutation, acetoacetate production is stimulated, the Winship researchers had found. On top of that, acetoacetate binds the mutated B-raf protein and promotes its oncogenic activity, forming a cycle of positive feedback.

    "...The Winship researchers wanted to test whether V600E cancer cells would respond to external acetoacetate. A ketogenic diet with very low carbohydrates, like an Atkins diet, can cause acetoacetate levels in the body to rise. Fasting can also trigger the same effect. Lipid-lowering agents commonly used to treat high cholesterol, such as statins (in this case, fluvastatin), niacin and fenofibrate, could slow the expansion of V600E tumors in mice, even when they were fed a normal diet. Those drugs reduced acetoacetate levels, and when the researchers injected acetoacetate to compensate, tumor growth sped up again."


    http://www.cell.com/cell-metabolism/abstract/S1550-4131(16)30643-X
    "...We chose three drugs that are clinically used to treat hypercholesterolemia: fluvastatin, which belongs to a class of cholesterol-lowering statins that are HMG-CoA reductase inhibitors (Avis et al., 2007); niacin (a.k.a. vitamin B3), which lowers triglycerides and is also clinically used to treat cardiovascular patients not taking a statin (Jacobson et al., 1994); and fenofibrate, a fibric acid derivative that also lowers triglycerides (Superko, 1989). We found that fluvastatin and niacin treatment effectively attenuated tumor growth potential of BRAF V600E-expressing A375 cells in xenograft mice; this could be reversed by intraperitoneal injection with acetoacetate (Figures 3A, top, and S4A, left)...Consistent with these findings, treatment with fluvastatin, niacin, or fenofibrate resulted in reduced serum levels of acetoacetate, but not b-hydroxybutyrate, in mice(Figures 3B and 3C, respectively), while acetoacetate injection rescued the decreased serum acetoacetate levels but did not affect 3HB levels."

    "...We next sought to determine whether functional inhibition of acetoacetate would attenuate BRAF V600E tumor growth. We examined a group of commercially available acetoacetate analogs and found that dehydroacetic acid (DHAA) (Figure 4A) is an inhibitory homolog of acetoacetate."
    "...Consistent with these findings, DHAA treatment for 3.5 weeks effectively inhibited tumor growth rates, sizes, and masses in nude mice with BRAF V600E-expressing human melanoma A2058 and A375 cell xenografts, but not in mice carrying control xenografts derived from HMCB cells expressing NRAS Q61K (Figures 6A and S6A)."
    "...DHAA is a synthetic organic compound that is used mostly as a fungicide and bactericide (Stedman et al., 1954); it shows little to no clinical toxicity or irritating potential and has been safely used in skin-care products. Consistently, chronic injection of DHAA to nude mice for 4 weeks revealed that 200 mg/kg/day administered intraperitoneally is a well-tolerated dose that did not cause notable differences in histopathological analyses and weights of diverse organs (Figures S6C and S6D, respectively). Moreover, chronic treatment with DHAA had no obvious effect on the mouse gut microbiome, as evidenced by an unaltered total-DNA amount extracted from bacteria in mouse feces; this suggested no change in total bacterial number in the mouse gut (Figure S6E), and by altered proportions but no loss of any components of the gut microbiota (Figure S6F). DHAA treatment did not alter complete blood counts (CBC) or hematopoietic properties in representative A375 xenograft mice compared to the water-treated group (Table S1). These results together suggest that DHAA treatment does not cause obvious toxicity in vivo."
    "...Further studies revealed that the inhibitory effect of DHAA treatment on tumor growth potential of A375 cells in xenograft mice was not reversed by intraperitoneal injection with acetoacetate (Figure 6G) despite increased serum levels of acetoacetate in DHAA-treated mice that received acetoacetate injection (Figure 6H). DHAA treatment did not affect serum levels of 3HB, cholesterol, or glucose in mice in either the presence or the absence of acetoacetate injection (Figures 6I, 6J, and S6G, respectively). Consistently, acetoacetate injection did not reverse the inhibitory effects of DHAA on phosphorylation of MEK1 and ERK1/2 (Figure 6K), BRAF V600E-MEK1 binding (Figure 6L), or cell proliferation rates assessed by IHC staining of Ki67 (Figures 6M and S6H) in tumors derived from A375 cells in mice. These data are consistent with previous results (Figures 5D–5E, 5I, and S5C) showing that acetoacetate was insufficient to reverse the effect of DHAA on BRAF V600E-expressing cells."
    "...Consistent with our findings presented above, we found that treatment with a high-fat diet promoted—while DHAA alone inhibited—tumor growth rates, sizes, and masses in nude mice with BRAF V600E-expressing A2058 or A375 cell xenografts; co-treatment with DHAA effectively reversed the enhanced tumor growth potential of A2058 or A375 cells in xenograft mice fed with a high-fat diet (Figures 7A and S7A)."


    An interesting side note from the above study is the use of a functional antagonist to acetoacetate instead of inhibiting its synthesis with niacin/niacinamide. The functional inhibitor used was dehydroacetic acid (DHAA) and it was very effective in curbing tumor growth when used in the same doses as niacin - i.e. HED of 15mg/kg. What is more important, just like niacin / niacinamide, DHAA was able to curb tumor growth even in the presence of high-fat diet and even injecting additional acetoacetate was not able to reverse the beneficial effect of DHAA. Given that DHAA is widely used and has very well-known safety profile (unlike orlistat), and is cheaply available as OTC chemical / supplement it could become one of the alternatives for people who cannot get access to other chemical like mildronate or want to potentiate the effects of niacinamide.
    Dehydroacetic acid - Wikipedia"
     
  10. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,169
    Gender:
    Male
    Location:
    USA / Europe
    That study used mutated tumor cells. I sent it to Ray back when that thread was posted and he said that the increase in acetoacetate production is protective, and that the benefit of niacin was due to lowering lipolysis and improving glucose metabolism. The lowering of acetoacetate by niacin, according to Peat, was just a corollary of it lowering lipolysis. As far as DHAA, he said it likely has other mechanism of action because as the study itself showed, adding acetoacetate to DHAA treatment did NOT reverse its beneficial effects.
    So, I don't see a problem combining acetoacetate with niacinamide. In fact, they should be synergistic.
     
  11. Lee Simeon

    Lee Simeon Member

    Joined:
    Mar 3, 2017
    Messages:
    232
    Gender:
    Male
    Do you have any experience regarding the topical absorption rate? Recently ordered and not sure if I will chose to do topical or oral. Was curious just because it seems like it does not contain any solvents like SFA ester or MCT.
     
  12. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,169
    Gender:
    Male
    Location:
    USA / Europe
    Ethyl acetoacetate itself is a powerful penetration enhancer, so it absorbs quite well through the skin. That is why we use it as one of the solvents in some other products. It is listed s FEMA 2415 on the label. As far as absorption, I feel about the same from using the same dose topically or orally. The topical route takes longer to manifest systemically though, maybe about 30min.
     
  13. GAF

    GAF Member

    Joined:
    Dec 28, 2014
    Messages:
    535
    Gender:
    Male
    Occupation:
    CPA
    Location:
    Dallas Texas
    Day 2 - 20 Drop oral first thing this morning in a shot glass of OJ. All day energy and wakefulness and focus (snacks required).

    GF....4 drops on arm in the morning...she was good all day.

    Now, going out dancing.

    Good stuff so far. Slept good last nite.
     
  14. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,169
    Gender:
    Male
    Location:
    USA / Europe
    Excellent, thanks for sharing!
     
  15. GAF

    GAF Member

    Joined:
    Dec 28, 2014
    Messages:
    535
    Gender:
    Male
    Occupation:
    CPA
    Location:
    Dallas Texas
    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.
     
  16. Steven Bussinger

    Steven Bussinger Member

    Joined:
    Oct 8, 2016
    Messages:
    266
    Gender:
    Male
    Location:
    Colorado, USA
    I just wanted to thank Haidut for his outstanding research here.
     
  17. nwo2012

    nwo2012 Member

    Joined:
    Aug 28, 2012
    Messages:
    958
    Narouz in disguise?
    Thats the only person who writes exactly this way.
     
  18. nwo2012

    nwo2012 Member

    Joined:
    Aug 28, 2012
    Messages:
    958
    Waiting on my 2 bottles making it to Oz. Then the experiments shall begin.
     
  19. debored13

    debored13 Member

    Joined:
    Nov 27, 2017
    Messages:
    664
    Gender:
    Male
    Widely known may have been a stretch , discussed in this thread Pyruvate Dehydrogenase Deficiencies and Cures?
    And also on Reddit /nootropics there were people trying to find ethyl pyruvate , which they had got in gas station energy drinks awhile ago
     
  20. tallglass13

    tallglass13 Member

    Joined:
    Dec 29, 2015
    Messages:
    288
    Gender:
    Male
    Occupation:
    Registered Nurse
    @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?
     
Loading...