Nemo

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From OP: "EP also exerts anti-apoptotic effects, increases heme oxygenase-1 expression..." which pyruvate itself doesn't do.

RP wrote that heme oxygenase produces carbon monoxide and that its production is stimulated by estrogen and pituitary hormones like ACTH, prolactin, etc. which obviously are not good.

I appreciate your posting your concern, lampofred. I always want to hear concerns like this.

I know that when I've tried to take Pyrucet daily for an extended period, even at a very low dose, it makes me manic.

But if you're coming out of something really bad, like cancer, there's nothing else like it. You don't need the official cancer diagnosis to know you're in serious trouble. Then you take this and you know you've escaped, at least for a while.

Same thing if you neglected to take D3 and thyroid all winter and at the end of the winter you find yourself in a serious hole.

So I wouldn't try to use this as a replacement for thyroid or progesterone but if you're in serious trouble, it's very nice to have around to help you regroup.

Edit: Since HO-1 is a heat shock protein, here is Ray Peat on how heat shock proteins work and at what cost (starting at 20:85 with an important summary at roughly 27:00).

 
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Mito

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From OP: "EP also exerts anti-apoptotic effects, increases heme oxygenase-1 expression..." which pyruvate itself doesn't do.

RP wrote that heme oxygenase produces carbon monoxide and that its production is stimulated by estrogen and pituitary hormones like ACTH, prolactin, etc. which obviously are not good.

I am wondering if this product is similar to 5a-DHP, concerning which Dr. Peat said that although progesterone itself its very good, supplementing its derivative product might have unintended consequences. Similarly, although pyruvate itself is very good, supplementing a derivative might have unintended consequences.

I am not criticizing Idea Labs, I appreciate and use many of its other products, but I think some of these are more in the direction of performance-enhancement than health-promoting and so might be unsafe.
Heme oxygenase-1 (HO-1) is a Nrf2-regulated gene that plays a critical role in the prevention of vascular inflammation. It is the inducible isoform of HO, responsible for the oxidative cleavage of heme groups leading to the generation of biliverdin, carbon monoxide, and release of ferrous iron.”
 

miraddo

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Heme oxygenase-1 (HO-1) is a Nrf2-regulated gene that plays a critical role in the prevention of vascular inflammation. It is the inducible isoform of HO, responsible for the oxidative cleavage of heme groups leading to the generation of biliverdin, carbon monoxide, and release of ferrous iron.”

So this is a good or bad thing? I find this to be a great supplement and dont feel it has any downsides apart from rashes which have now subsided with continued use and good nutrition.
 

Mito

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So this is a good or bad thing? I find this to be a great supplement and dont feel it has any downsides apart from rashes which have now subsided with continued use and good nutrition.
If Pyrucet increases Heme oxygenase-1, that seems beneficial according to that study. Peat was probably referring to the inducible isoform of heme oxygenase which is bad for all the reasons Peat stated.
 

Jam

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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.
I took my first 10 drops of this (topical) mid-morning after a carb-heavy (close to 70g) breakfast. An hour or so before lunch I measured my ketones and was at 0.2ppm, which is not sky-high but higher than I have ever measured, even at the end of a very low-carb (30g total) day.
 
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Jam

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I took a second 10-drop dose (oral this time) with lunch a couple hours ago, and have felt absolutely no effects. Will try the full dose tomorrow, but I'm wondering if someone who already has a robust oxidative metabolism would notice any acute benefits from Pyrucet.
 
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I took a second 10-drop dose (oral this time) with lunch a couple hours ago, and have felt absolutely no effects. Will try the full dose tomorrow, but I'm wondering if someone who already has a robust oxidative metabolism would notice any acute benefits from Pyrucet.
I am taking 10 drops for 15 days so far and no effects.

To be honest once I felt kind of like sickish and I took 10 drops in orange juice and felt better but other than that no effects.

I still have blurry eyes, random body aches and chest pains, I don't feel anything specific except maybe not being sensitive to bright daylight as much.

For the past 4 days I've been taking it twice a day: 10 drops 2x a day in orange juice. Still no effects except the others that I've mention.

@haidut Do you know if acidity in orange juice would diminish its effects? What's the best way to use the product. I've read through all the pages but I might have missed something.

Also I've been getting more pimples on my nose and face after eating some fats which I didn't have since high school. Would you say there is an adjustment period from body switching to oxidizing sugar instead of fats and what happens to the dietary fats we consume if we force the body to burn sugar?

I'm so sorry if this question sound absurd :)
 

Jam

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I took my first 10 drops of this (topical) mid-morning after a carb-heavy (close to 70g) breakfast. An hour or so before lunch I measured my ketones and was at 0.2ppm, which is not sky-high but higher than I have ever measured, even at the end of a very low-carb (30g total) day.
I just measured my ketones again, and the interesting thing is that, after a high-protein, low-carb (an apple was the only source) lunch and 10 drops of oral Pyrucet. my ketones are now so low as to not register. I have not registered any differences whatsoever in my blood glucose today that I'm on Pyrucet.
 

Nemo

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If Pyrucet increases Heme oxygenase-1, that seems beneficial according to that study. Peat was probably referring to the inducible isoform of heme oxygenase which is bad for all the reasons Peat stated.

Mito, thank you for this.
 

truegrit

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I took my first 10 drops of this (topical) mid-morning after a carb-heavy (close to 70g) breakfast. An hour or so before lunch I measured my ketones and was at 0.2ppm, which is not sky-high but higher than I have ever measured, even at the end of a very low-carb (30g total) day.
(Ethyl) AcAc is a ketone. So that makes sense and doesn't contradict what I posted. A non-trivial % of it gets metabolized to BHB, as well.
 

Jam

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(Ethyl) AcAc is a ketone. So that makes sense and doesn't contradict what I posted. A non-trivial % of it gets metabolized to BHB, as well.
Why so defensive? First off, this is proof that the product is being absorbed quite well, topically. Furthermore, I'm positing that taking Pyrucet on a high saturated fat diet will cause absolutely no issues, as some seem to be implying. I won't get into too much detail for the time being (also because I'm not 100% convinced of my theory just yet), but I plan to eat very low carb tomorrow and will then take a full dose of Pyrucet in one shot the following morning, while continuing to eat my typical high SFA diet, all in the name of science. Not only do I doubt that it will have any effect whatsoever on my blood sugar, but it will very likely not make me ravenously hungry between meals either. All this because I'm more interested in the anti-inflammatory and ant-biotic/biofilm-busting properties of this product, and the bit of scare-mongering in this thread was putting me off. I believe that the purported FAO inhibition only applies to *excess* FAO (especially of PUFA), but not to physiological FAO (especially of SFA), in vivo, with regular dosages.
 

Jam

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Effects of step-wise increases in dietary carbohydrate on circulating saturated Fatty acids and palmitoleic Acid in adults with metabolic syndrome

This further reinforces my belief that inhibiting excess free fatty acids in general would have pretty much no effect in a metabolically healthy person on a low-medium carb / high saturated fat diet such as mine.
I sort of accelerated my experiment and decided to eat another very low-carb meal for dinner last night, instead of waiting an extra day. I had a total of 80g of carbs yesterday, of which close to 70g for breakfast. This morning on waking, after a 12h fast, I was beginning to produce some ketones. I then had a full dose of Pyrucet with my normal breakfast including an orange, whole milk, some parmesan and 2 eggs, but skipped the usual honey. Three hours later, and I can detect no effects whatsoever, am not hungry, and my blood glucose (via CGM) has not deviated.
I can see this product as being very useful for people with some degree of metabolic syndrome on the SAD.
By default, a metabolically healthy person on a healthy (low PUFA) diet would never have excessive circulating FFA levels. On the SAD, though, eating excess fat + carbs, there would definitely be a bunch of FFA backed up in circulation with no place to go (with increasing systemic insulin resistance).
 
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Nemo

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Would you say there is an adjustment period from body switching to oxidizing sugar instead of fats and what happens to the dietary fats we consume if we force the body to burn sugar?

I noticed I started excreting dietary fats.
 

Mito

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Ethyl Pyruvate as a Potential Defense Intervention against Cytokine Storm in COVID-19?​

Abstract​

COVID-19 is a deadly pandemic and has resulted in a huge loss of money and life in the past few months. It is well known that the SARS-CoV-2 gene mutates relatively slowly as compared to other viruses but still may create hurdles in developing vaccines. Therefore, there is a need to develop alternative routes for its management and treatment of COVID-19. Based on the severity of viral infection in COVID-19 patients, critically ill patients (∼5%, with old age, and comorbidities) are at high risk of morbidities. The reason for this severity in such patients is attributed to "misleading cytokine storm", which produces ARDS and results in the deaths of critically ill patients. In this connection, ethyl pyruvate (EP) controls these cytokines/chemokines, is an anti-inflammatory agent, and possesses a protective effect on the lungs, brain, heart, and mitochondria against various injuries. Considering these facts, we propose that the site-selective EP formulations (especially aerosols) could be the ultimate adjuvant therapy for the regulation of misleading cytokine storm in severely affected COVID-19 patients and could reduce the mortalities.
 
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I noticed I started excreting dietary fats.
It's funny how it started to happen to me to 2 days in a row after consuming full dose (25 drops in OJ)

Somehow it doesn't feel like a useful or "helpful" thing :)

I have some strange stomach sensation similar to the one when I went on the carnivore diet and the first 2-3 days I had like watery stool.
 

Nemo

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It's funny how it started to happen to me to 2 days in a row after consuming full dose (25 drops in OJ)

Somehow it doesn't feel like a useful or "helpful" thing :)

I have some strange stomach sensation similar to the one when I went on the carnivore diet and the first 2-3 days I had like watery stool.

Exactly.

I always take a break from it at this point.
 

hibiskus

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Did anyone who used the product have symptoms one could connect to the glutathione depletion. I am pretty interested in the product but concerned that the glutathione depletion could have some unwanted effects. And does someone know by what actual mechanism ethyl pyruvate depletes glutathione.
 
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