OP
haidut

haidut

Member
Forum Supporter
Joined
Mar 18, 2013
Messages
19,798
Location
USA / Europe
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.

Bioavailability is how much gets absorbed. Peak serum is probably what they call Cmax in studies. Bioavaiability for pyruvate and acetoacetate is high, as studies found that less then 0.1% of administered dose of calcium pyruvate gets excreted in urine/stool. So the rest is absorbed and I don't see why it won't be the same for EP/EA.
Another study with calcium pyruvate found that Cmax was achieved after 180min (3h). Half life for calcium pyruvate seems to be about 5 hours.
The bioavailability of calcium in the form of pyruvate, carbonate, citrate–malate in healthy postmenopausal women
 

SB4

Member
Joined
Sep 25, 2016
Messages
288
Bioavailability is how much gets absorbed. Peak serum is probably what they call Cmax in studies. Bioavaiability for pyruvate and acetoacetate is high, as studies found that less then 0.1% of administered dose of calcium pyruvate gets excreted in urine/stool. So the rest is absorbed and I don't see why it won't be the same for EP/EA.
Another study with calcium pyruvate found that Cmax was achieved after 180min (3h). Half life for calcium pyruvate seems to be about 5 hours.
The bioavailability of calcium in the form of pyruvate, carbonate, citrate–malate in healthy postmenopausal women
Thanks. I have used pyrucet for the last 3 days at recommend dose. Perhaps increase in hunger though it's early days yet. I am mainly looking for it to reduce heart pounding / lactic acid build up post carbs which brings me on to my next question.

What I am wandering is about taking big doses of ethyl acetoacetate, say 15 grams with food. That would be something like 3grams ethanol (???) and 12g acetoacetate. This would be close to supplying the same amount of acetyl CoA as 1tbsp (14g) of MCT oil, assuming the ethyl acetoacetate gets broken down into acetoacetate.

I would like to do this as MCT oil has helped big time with my post carb symptoms however it causing GI upset even at 1tbsp. I am thinking it helps by forcing pyruvate to go to oxaloacetate thanks to oversupply of acetylcoA (in the liver?)

My problem with this line of thinking is, if it was this easy to supply exogenous ketones in the form of ethyl acetoacetate then why are supplement companies going to great lengths to create foul tasting exogenous ketone products in the form of ketone salts?

Also would the ethyl acetoacetate cause problems in this high of a dose?
 

Lee Simeon

Member
Joined
Mar 3, 2017
Messages
494
Purycet.png
 

Vinero

Member
Joined
Feb 20, 2013
Messages
1,551
Age
32
Location
Netherlands
Took my first dose today (20 drops). I took it in the morning after eating fried eggs, coke, coffee and aspirin. It burns.. very much. It feels like I'm drinking hard alcohol. I needed some water to stop the burning in my mouth.

After that, I went out for a walk outside. I felt very relaxed, as if my GABA levels were raised. It reminded me a bit of phenibut, which is a GABA-B agonist. I like the feeling of Pyrucet. It's not overwhelming and weird like Diamant can be, but subtle and relaxing, like having one beer or something.
 

Jsaute21

Member
Joined
Sep 3, 2016
Messages
1,344
Took my first dose today (20 drops). I took it in the morning after eating fried eggs, coke, coffee and aspirin. It burns.. very much. It feels like I'm drinking hard alcohol. I needed some water to stop the burning in my mouth.

After that, I went out for a walk outside. I felt very relaxed, as if my GABA levels were raised. It reminded me a bit of phenibut, which is a GABA-B agonist. I like the feeling of Pyrucet. It's not overwhelming and weird like Diamant can be, but subtle and relaxing, like having one beer or something.

Yeah, the taste is shocking at first. Burns momentarily but the after taste is actually almost pleasant and freshens up the breath i've noticed. I worked out Wednesday night after taking it and i felt like i could work out comfortably for 2-3 hours at a decently high intensity.
 

Vinero

Member
Joined
Feb 20, 2013
Messages
1,551
Age
32
Location
Netherlands
Wow. I just came back from the gym and had much more energy than usual. I was also much more hungry when I came back and could eat more food. I am beginning to like this Pyrucet very much.
 

mirc12354

Member
Joined
Jan 8, 2016
Messages
279
Would anyone who took Mildronate as well as Pyrucet mind to compare the experience with both? Similarities, differences?
 

SB4

Member
Joined
Sep 25, 2016
Messages
288
Anyone help me out here? For ethyl acetoacetate, LD50 Oral - rat - 3,980 mg/kg. Convert to human dose /8 = 500mg/kg. Convert to average body weight x80kg = 40g LD50 for humans. That seems very low for something than is basically ethanol and ketone body. Is this what it breaks down into? Am I going wrong somewhere here?
 

SB4

Member
Joined
Sep 25, 2016
Messages
288
Why don't these supplement companies use ethyl beta hydroxybutyrate instead of struggling to get ketone esters and salts to work? There has to be something I am missing here. Is it because the ethyl form has other effects like described in this thread and this could cause problems where the salts and esters don't?
 

truegrit

Member
Joined
Oct 6, 2017
Messages
17
Why don't these supplement companies use ethyl beta hydroxybutyrate instead of struggling to get ketone esters and salts to work? There has to be something I am missing here. Is it because the ethyl form has other effects like described in this thread and this could cause problems where the salts and esters don't?

I think you're missing a few things that are fairly obvious: @haidut's aim with this product isn't to raise ketone levels in the body or push the body towards ketosis or spare glucose - quite the opposite actually. Then, there are practical considerations. Ketone esters - either BHB or acetoacetate - taste abhorrent and wouldn't fare well commercially for that reason. Also, almost without exception, most commercial ketone products are powdered.

The keto zealots are obsessed with being "fat burners" and would run from a substance that inhibits FAO. Their express purpose is to turn on FAO and spare glucose; they've concluded, however misguidedly, that this is preferable.

Now, a lot of the above is semantics. If you look at this blog post from Peter Attia, he documents how an exogenous ketone bolus (15.6g BHB) affects his respiratory quotient, fat oxidation, glucose oxidation, and more during strenuous exercise and even he sort of ties himself up with the data.

Here's a few excerpts from the linked post above:
So, for this second effort (the test set) my body did about 5% less mechanical work, while oxidizing about 25% less of my own fat [emphasis mine]. The majority of this difference, I assume, is from the utilization of the exogenous BHB, and not glucose (again, I will address below what I think is happening with glucose levels).

The energy necessary to perform the mechanical work did not appear to change much between tests, though the amount of oxygen utilization and fat oxidation did go down measurably [emphasis mine]. The latter finding is not surprising since the body was not sitting on an abundant and available source of BHB—there was less need to make BHB “the old fashioned way.”

As seen in this exercise,
glucose tends to fall quite precipitously following exogenous ketone ingestions [emphasis mine]. Without exception, every time I ingested these compounds (which I’ve probably done a total of 25 to 30 times), my glucose would fall, sometimes as low as 3 mM (just below 60 mg/dL). Despite this, I never felt symptomatic from hypoglycemia. Richard Veech (NIH) one of the pioneers of exogenous ketones, has suggested this phenomenon is the result of the ketones activating pyruvate dehydogenase (PDH), which enhances insulin-mediated glucose uptake [emphasis mine]. (At some point I will also write a post on Alzheimer’s disease, which almost always involves sluggish PDH activity —in animal models acute bolus of insulin transiently improves symptoms and administration of exogenous ketones does the same, even without glucose.)

Finally, these compounds seemed to have a profound impact on my appetite
(they produced a strong tendency towards appetite suppression) [emphasis mine].

There's a lot to unpack here. I think it's somewhat symptomatic of the old if you're a hammer, everything's a nail problem. Attia is squarely in the low-carb camp. He's philosophically opposed to almost everything Peat espouses. But you can see from his post that his experience doesn't quite square with his philosophy. He readily writes off the fact that his fat oxidation actually went down after ingesting BHB. He also implicates increased PDH activity for the increase in glucose oxidation (uptake?) - something he and Haidut agree on. Attia and Haidut also seem to agree that keto acids out-compete fatty acids for oxidation and this is largely responsible for the resultant decrease in FAO. And then the last bit about appetite: Attia says BHB salts decrease his appetite. My experience, as well as that of others in this thread, is that Pyrucet produces a rapid uptick in appetite - probably explained by falling blood glucose from the increased PDH. Here again, the opposite conclusion driven by the exact same effect.

I also want to disclaim that my goal with this post is not to prop up Dr. Attia, not at all. I wanted to use him more as a foil so everyone could see how a supplement that ostensibly does the same thing can get claimed as equally therapeutic by the keto crowd.

There are some things here that are still a bit over my head (I'm trying to get a handle on the interaction between malonyl-CoA and CPT-1) and obviously almost this entire post is meant to elucidate common ground between ethyl acetoacetate and BHB salts (because this is what the poster inquired about). The wild card is how the concomitant administration of the EP in Pyrucet magnifies or distorts the effect.

Anway, stirring the pot - wanted to get some discussion going.
 

SB4

Member
Joined
Sep 25, 2016
Messages
288
@truegrit thanks for the reply. I have previously read that blog post but it doesn't address my question of why supplement compainies are not trying to sell ethyl acetoacetate / beta hydroxybutyrate as exogenous ketones. I feel there must be a reason for this.

I should have been more clear in my posts. I do understand the intentions of hadiut in the use of this product however my intentions are a little different thanks to my illness.

I have decent reason to suspect a problem with PDH due to research links and my improved carb tolerance with MCT oil. I have tried things that activate PDH in the past (Thiamine, ALA, Mg, Dichloroacatate) with only mild success. I suspect the moderate success I have with MCT is that it is allowing me to bypass PDH and funnel carbs down to oxaloacetate.

I would do a lot better if I could find something more effective than MCT oil as anything over 1tbsp causes to much digestive upset. This is why I am wandering if higher doses of ethyl acetoacetate would be safe / effective.
 

truegrit

Member
Joined
Oct 6, 2017
Messages
17
@truegrit thanks for the reply. I have previously read that blog post but it doesn't address my question of why supplement compainies are not trying to sell ethyl acetoacetate / beta hydroxybutyrate as exogenous ketones. I feel there must be a reason for this.

I should have been more clear in my posts. I do understand the intentions of hadiut in the use of this product however my intentions are a little different thanks to my illness.

I have decent reason to suspect a problem with PDH due to research links and my improved carb tolerance with MCT oil. I have tried things that activate PDH in the past (Thiamine, ALA, Mg, Dichloroacatate) with only mild success. I suspect the moderate success I have with MCT is that it is allowing me to bypass PDH and funnel carbs down to oxaloacetate.

I would do a lot better if I could find something more effective than MCT oil as anything over 1tbsp causes to much digestive upset. This is why I am wandering if higher doses of ethyl acetoacetate would be safe / effective.

Then, there are practical considerations. Ketone esters - either BHB or acetoacetate - taste abhorrent and wouldn't fare well commercially for that reason. Also, almost without exception, most commercial ketone products are powdered.

^^ I believe it's largely due to this. And I believe the esters (rather than the salts) have been shown to fairly predictably cause GI distress at sufficiently large doses. I'm telling you though - you underestimate just how niche something like ethyl acetoacetate would be if sold as a liquid oral supplement. The mass market would utterly reject that; there are no dollars in it. Powdered products that taste good and travel well are what drive mainstream supplements. Most of these people can't even articulate why they want to be in ketosis - they just know it's buzzworthy and has something to do with weight loss.
 

Mauritio

Member
Joined
Feb 26, 2018
Messages
5,669
As this should have the same/ similar effects as Mildronate ,has anybody tried it and seen enhanced endurance or can compare it to Mildronate ?
 

Mauritio

Member
Joined
Feb 26, 2018
Messages
5,669
Here are some reviews from the internet for Mildronate , I have already ordered Pyrucet and will probably order Mildronate to compare them,but as I stated Pyrucet should work similar to that :


"I am am a student who exercises in the early morning. Mildronate is a fantastic addition to my training. My endurance is significantly improved and I have an overall sharper mental focus over the course of the day. Highly recommended."

"There is no question in my mind that it has improved my lung capacity and energy, as well as my overall health. I will continue to use this product as well as others that I am now ordering. Thank you Cosmic! "

"So far, the beat drug to improve energy, focus, mood and sleep"

"So I bought this not really as a nootropic, but for a friend who has vascular/circulation issues. It has helped her immensely, particularly in circulation to her hands and fingers ("Raynaud's disease"). Usually, when it gets cold at all, her fingers will turn completely white and become cold. Her nailbeds had become purple/black from the constant lack of oxygen, and she was very self-conscious of her hands in public. Now, they barely ever turn color, and if they start they almost always turn back. It's been only a month and a half and her nailbeds have also almost completely healed. It also seems to have helped with her brain function. I'm not saying it will work for everyone, but for her it has been almost a miracle drug."


"It helps to clear the "fog" that many elite athletes feel from pushing themselves to the limit day in and day out. Very mild caffeine-like effect without the typical caffeine anxiety. It not only allows me to recover physically and mentally from workouts, it absolutely boosts brain functioning (concentration, clearer thought processes, etc.). I truly cannot comprehend how something that can improve quality of life so greatly is not universally available. My only complaint would be that it is not being manufactured outside of RU, but cosmic nootropic has very fortunately solved that problem."

"As for my experience. It's subtle, but profound. It takes time for this to work and needs to be taken on an empty stomach. I've only had a few doses so far, but I can already tell it has great potential for a life-long way to prevent heart attacks and strokes. Not to mention, it gives me a subtle boost of energy. I have been dealing with sleep apnea issues on and off for some time. The way this product works, it has helped restore the circulation in my body such that I wake up not feeling as wiped out as I used to when I would sleep without breathing as well. So while it's not a cure for sleep apnea, it works to help my body protect itself against the damage that can be caused by oxygen deprivation. If I only had enough money to buy one nootropic or cerebral protector, it would be spent on mildronate. It's simple, non-toxic, and not only makes me feel a bit of energy, but is also giving me peace of mind knowing that my vascular system is being nourished."

"After getting a recommendation from my Ukrainian friend, I gave meldonium a go. The effects are somewhat unpredictable so far, but I feel with further research and usage i will be able to predict them. I have taken this at my workplace (machinist job) with minimal sleep and it provided a great deal of energy. It was like I was wide awake and I was just another machine!"

"All my life I'm stumbling. About a year ago, I began taking mildronate, in order to increase efficiency. I noticed that after taking the drug, I became significantly less stutter. The stammering did not completely disappear, but it became much less. The admission of mildronate I combined with the magnesium-potassium complex for the heart muscle "Asparcam". But I think that the merit in reducing stuttering is associated with the reception of mildronate. The effect of the drug begins about a week after admission. Sorry for bad english - i use google translate for writting in English."


"I play ice hockey, tennis and I do weights training and yoga. I have personally taken Meldonium from Grinkers before weights and yoga training (2 x 250mg) and before ice hockey, and the benefits are immediate : more energy, no hunger, feeling light, as if my body was not heavy, also feeling really concentrate and aware and brain's functions seems enhanced. I could also add that this drug, make you not wanna lose, seems like it has a mental effect that keep you pushing more and refusing to lose or giving up and makes you wanna give your best until the end even in a losing game/match up. I bough from popular online auction site ... Its surely a PED, I can confirm it. Also, the performance effects can last up to 2 days. The dose is 500mg to 1000mg before training, once I have enough guts to try 1000mg, I will post again..."
 

golder

Member
Joined
May 10, 2018
Messages
2,851
As this should have the same/ similar effects as Mildronate ,has anybody tried it and seen enhanced endurance or can compare it to Mildronate ?
Does mildronate have any toxicity issues? I’m keen to try some but I want to know more about dosages/toxicity etc in order to safely compare the two.
 

Mauritio

Member
Joined
Feb 26, 2018
Messages
5,669

ravensburger

Member
Joined
Jun 14, 2017
Messages
22
I have taken Mildronate/Meldonium before for two months on/one month off. 1000mg-2000mg a day depending if I was training or not.

I just ordered Pyrucet and will let you know if there is any difference.

Mildronate helped my breathing, endurance as an athlete, and energy. The most profound effect was the mood enhancement. I was incredibly happy and positive all the time.

However, there were side effects that I believe were a result of all the additives in the pills. Titanium Dioxide was (I believe) the main irritating compound and I had significant stomach distress and nausea after taking it for a while. I discontinued using it because of this effect.

I’m hoping Pyrucet is comparable in its effects because I truly loved the feeling of Meldonium.
 

Mauritio

Member
Joined
Feb 26, 2018
Messages
5,669
I have taken Mildronate/Meldonium before for two months on/one month off. 1000mg-2000mg a day depending if I was training or not.

I just ordered Pyrucet and will let you know if there is any difference.

Mildronate helped my breathing, endurance as an athlete, and energy. The most profound effect was the mood enhancement. I was incredibly happy and positive all the time.

However, there were side effects that I believe were a result of all the additives in the pills. Titanium Dioxide was (I believe) the main irritating compound and I had significant stomach distress and nausea after taking it for a while. I discontinued using it because of this effect.

I’m hoping Pyrucet is comparable in its effects because I truly loved the feeling of Meldonium.
Thanks, looking forward to your review !
 

golder

Member
Joined
May 10, 2018
Messages
2,851
I have taken Mildronate/Meldonium before for two months on/one month off. 1000mg-2000mg a day depending if I was training or not.

I just ordered Pyrucet and will let you know if there is any difference.

Mildronate helped my breathing, endurance as an athlete, and energy. The most profound effect was the mood enhancement. I was incredibly happy and positive all the time.

However, there were side effects that I believe were a result of all the additives in the pills. Titanium Dioxide was (I believe) the main irritating compound and I had significant stomach distress and nausea after taking it for a while. I discontinued using it because of this effect.

I’m hoping Pyrucet is comparable in its effects because I truly loved the feeling of Meldonium.

Very much looking forward to your review as well, please don’t forget, however little you can add.
 

Similar threads

Back
Top Bottom