RP Email Advice Comment: 5-Alpha Dihydroprogesterone

goodandevil

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Q: "He's got a new 5a-dihydroprogesterone, just hit the streets today."

Ray: "Pregnenolone, DHEA, and progesterone are basic stabilizing molecules, and I think it’s dangerous to use novel substances that are likely to interact with those, in the absence of large amounts of preliminary experimentation with animals and in vitro."
 
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Lol, why do you assume he knows him?
 

Agent207

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Wait a moment, why you ask Ray that? This product is not supposed to use in ourselves but for research with our hamsters.

That's just what Ray replied, research first to prove safety.
 

Makrosky

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Wait a moment, why you ask Ray that? This product is not supposed to use in ourselves but for research with our hamsters.

That's just what Ray replied, research first to prove safety.
Because we care so much about or beloved hamsters...they are not disposable wistar rats, you know?
 

haidut

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Q: "He's got a new 5a-dihydroprogesterone, just hit the streets today."

Ray: "Pregnenolone, DHEA, and progesterone are basic stabilizing molecules, and I think it’s dangerous to use novel substances that are likely to interact with those, in the absence of large amounts of preliminary experimentation with animals and in vitro."

I suggest when asking Ray about a substance to send him at least the studies I have posted. Obviously, if he has not seen studies about it he may respond that way. We can't expect him to know off-hand about every steroid out there. I also don't expect him to be approving of everything I release. That is why I provide the evidence that I found so far. Before I release a product I do look up studies on safety and effects, so obviously this is why I am posting them. So, please copy and paste the studies I posted and if he has more to add then great.
Also, when asking him about a substance it would probably help to ask about the substance and not include references to me or any other vendor. No need to get the business side of things involved with the purely scientific questions. So, even if it is a question about something like Pansterone the questions could be "Hey Ray, what do you think about pregnenolone/DHEA dissolved in DMSO". IMO it helps to keep the conversation focused on the chemical and its effects and not mixed up the person/company behind a product in the conversation.
Just my 2c.
 
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haidut

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"Ray, what is a podcast?"

Yeah, I am not sure he knows me. I have sent him some supplements to try and have exchanged some emails but so do thousands of other people probably.
 

haidut

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What's wrong with using down streamed hormonal products ?

Nothing, that is why the pharma industry is all over allopregnanolone - i.e. immediate metabolite of 5a-DHP, which btw can convert back into 5a-DHP when given in higher doses. So, in effect, the safety of 5a-DHP has been indirectly studied in humans due to the clinical trials with high doses allopregnanolne, which elevates 5a-DHP levels.
 

haidut

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I think the only things that Ray Peat feels like actively recommending are those he has been using himself for a significant part of his life. For him this is a structural part of the way he investigates substances. So if like him, you wish to be an investigator of health, get some rats and experiment; if you just wish to be as him, then by all means don't try it, because you'll never hear him interested in something so particular.
 

goodandevil

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Nothing, that is why the pharma industry is all over allopregnanolone - i.e. immediate metabolite of 5a-DHP, which btw can convert back into 5a-DHP when given in higher doses. So, in effect, the safety of 5a-DHP has been indirectly studied in humans due to the clinical trials with high doses allopregnanolne, which elevates 5a-DHP levels.
@haidut
An endorsement from Big Pharma regarding a metabolite of 5a-DHP, but not 5a-DHP, is no guarantee of safety. Did Ray say something is safe if Big Pharma endorses it? No. Maybe it is safe but I feel your reasoning is tenuous. I didn't doctor Ray's words. I mentioned your new product in an unrelated email and told ray that I share his responses, that is what he told me. I am excited to hear you're switching from DMSO to tocopherols. I wish you success.
 

paymanz

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Why would he mention DHT?
He named basic stabilizing hormones,I thought DHT may be one of them.

Especially that you mentioned in a post that he doesn't reccomend DHEA anymore...

raypeatforum.com/community/threads/who-has-used-or-is-using-dht.11759/page-11#post-162380

DHT being second only to progesterone on his list:
https://raypeatforum.com/community/threads/who-has-used-or-is-using-dht.11759/page-9#post-161983
Who Has Used Or Is Using DHT?

Maybe DHT is one of those down stream hormones and it is why he didn't mentions it,he was speaking the basics!
 
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schultz

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I like these critical discussions but I can't help but feel you are going out of your way to denigrate Haidut, and setting Peat up to do it with you. Like saying "just hit the streets" as if Haidut is selling narcotics to kids or something.

Aside from that, I think with these types of specialty hormonal supplements it would be good to use caution. I also think it's good to use caution with any other supplement you use. Supplements are very fun to use and people can go overboard. With these downstream hormones the potential for causing problems does seem increased, compared to taking pregnenelone or progesterone for example, but I think the potential therapeutic action is also increased. That's why these supplements are so fun to try.... for our rats... because the effects are sometimes more noticeable. This could be helpful for someone who is in poor health and trying to break the cycle.

Ray has said it could be dangerous. This means - for me personally - start slowly, titrate up, be discerning. Better yet, get before and after blood work. Ray is very cautious about things, which is funny because mainstream people think he is crazy for recommending sugar, etc and saying negative things about fish oil. He's actually the least crazy "health guru" if you think about it.

@haidut How would 5a-dihydroprogesterone potentially interact with progesterone?
 

haidut

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@haidut
An endorsement from Big Pharma regarding a metabolite of 5a-DHP, but not 5a-DHP, is no guarantee of safety. Did Ray say something is safe if Big Pharma endorses it? No. Maybe it is safe but I feel your reasoning is tenuous. I didn't doctor Ray's words. I mentioned your new product in an unrelated email and told ray that I share his responses, that is what he told me. I am excited to hear you're switching from DMSO to tocopherols. I wish you success.

OK, I should have been more specific. Ray has favorably mentioned allopregnanolone and its properties in the brain. He has mentioned to a few people over email that using progesterone (as a precursor) to raise it can be therapeutic for a few neurodegenerative conditions and that it was allopregnanolone that was therapeutic. I would have actually gone with allopregnanolone as a product but feel it is too risky legally given the enormous commercial interest behind it and its synthetic offshoots.
Serotonin, depression, and aggression - The problem of brain energy.
"...The neurosteroid, allopregnanolone, for which progesterone is the precursor, facilitates the inhibitory action of GABA, which is known to be deficient in some disorders of mood and movement. This suggests that progesterone will be therapeutic in the movement disorders, as it is in various mood problems. Progesterone has some specific antiserotonin actions (e.g., Wu, et al., 2000)."

"...One of the many actions of the "SSRI" (such as fluoxetine, Prozac), which aren’t related to their effect on serotonin, is to increase the concentration of allopregnanolone in the brain, imitating the action of increased progesterone. Following this discovery, Lilly got Prozac approved as a treatment for premenstrual syndrome. Since the production of allopregnanolone and progesterone depends on the availability of pregnenolone and cholesterol, a low cholesterol level would be one of the factors making this an inappropriate way to treat PMS."

In this other article he has a study, where he has underlined the portions about allopregnanolone in a way that seems to again suggest he thinks it is beneficial.
Stem cells, cell culture, and culture: Issues in regeneration
"...Curr Alzheimer Res. 2006 Feb;3(1):11-7. Preclinical analyses of the therapeutic potential of allopregnanolone to promote neurogenesis in vitro and in vivo in transgenic mouse model of Alzheimer's disease. Brinton RD, Wang JM. "Herein, we present data to support a preclinical proof of concept for the therapeutic potential of allopregnanolone to promote neurogenesis. Our recent work has demonstrated that the neuroactive progesterone metabolite, allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), (APalpha) induced, in a dose dependent manner, a significant increase in proliferation of neuroprogenitor cells (NPCs) derived from the rat hippocampus and human neural stem cells (hNSM) derived from the cerebral cortex [1]." "The in vitro and in vivo neurogenic properties of APalpha coupled with a low molecular weight, easy penetration of the blood brain barrier and lack of toxicity, are key elements required for developing APalpha as a neurogenic / regenerative therapeutic for restoration of neurons in victims of Alzheimer's disease."

There is a ton of research behind allopregnanolone and it started even before Ray got into biology. The neurosteroids were researched heavily as general anesthetics and are actually approved as such in many countries. If you look at the main 5a-DHP thread I specifically mention that some of its metabolite are used for general anesthetics. See below.
Pregnanolone - Wikipedia
Alfaxalone - Wikipedia

Finally, it helps to keep in mind that 5a-DHP simply the intermediary step between progesterone and allopregnanolone. There is no other step, so it goes progesterone->5a-DHP->allopregnanolone. Both of these steroids are recognized as beneficial by Ray and 5a-DHP has nowhere to do but rapidly metabolize into allopregnanolone. Like I said before, you can't administer progesterone or allopregnanolone without raising 5a-DHP levels so to talk about them as beneficial but 5a-DHP as suspect requires some reason to do so. He did not say it is dangerous, he simply said it is dangerous to use a steroid without safety studies. I provided quite a few of these studies so I would like to hear his opinion once (and if) he sees/reads them. I understand that simply claiming Big Pharma is using allopregnanolone is not a good enough reason. So, again, that's why I provide studies for all of the products I release.
 

haidut

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I like these critical discussions but I can't help but feel you are going out of your way to denigrate Haidut, and setting Peat up to do it with you. Like saying "just hit the streets" as if Haidut is selling narcotics to kids or something.

Aside from that, I think with these types of specialty hormonal supplements it would be good to use caution. I also think it's good to use caution with any other supplement you use. Supplements are very fun to use and people can go overboard. With these downstream hormones the potential for causing problems does seem increased, compared to taking pregnenelone or progesterone for example, but I think the potential therapeutic action is also increased. That's why these supplements are so fun to try.... for our rats... because the effects are sometimes more noticeable. This could be helpful for someone who is in poor health and trying to break the cycle.

Ray has said it could be dangerous. This means - for me personally - start slowly, titrate up, be discerning. Better yet, get before and after blood work. Ray is very cautious about things, which is funny because mainstream people think he is crazy for recommending sugar, etc and saying negative things about fish oil. He's actually the least crazy "health guru" if you think about it.

@haidut How would 5a-dihydroprogesterone potentially interact with progesterone?

5a-DHP is a progestogen but a bit weaker than progesterone. So, it has not been shown to be able to displace progesterone from its "receptor" and as such interfere with progesterone's effects. Also, in one of the studies I posted in the main thread it was shown that 5a-DHP stimulates progesterone and pregnenolone synthesis. So, it does not seem to have a negative feedback mechanism but a positive one. The same is true for pregnenolone, and progesterone (i.e. they stimulate their own synthesis). Typically, when there is a positive feedback mechanism it suggests that the body would like to get more of that steroid. Finally, just like you said, the way the questions are asked matters. If it is asked in a way that suggests I just threw something on the street out there without much thought or consideration then of course Ray is going to react like that, especially when not being given any studies to consider (which he said are needed to make a proper decision). There are over 400 studies on PubMed focusing on 5a-DHP and the steroids derived from it. Clearly, to go over each and every one of them is not something that I can casually do in a few hours just for kicks. So I did my due diligence considering the available evidence and there certainly is available evidence (including for safety) for 5a-DHP. Hopefully Ray gets to see the studies and comment on this later on.
Thanks for bringing this up.
 

moriwatzi

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Ray is anticommercial (to a fault). The framing of the question "yo this new stuff just hit the streets today" alone will trigger him. And it is perfectly reasonable to warn against novel substances he probably hasn't read about yet in depth. Everyone buys these things at their own risk. The true method of knowledge is experiment.
 
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