PFS: 3a and 3b-HSD theory

[Jayvee]

It can definitely stack well with Lapodin. It's great against excess glutamate and lactate. But since you're getting results from gelatin, perhaps you rather benefit from NMDA agonist (glycine is an agonist). Piracetam, tianeptine, serine and sarcosine can also promote/restore the glutamate system.

Thanks do you think try them instead of Lapodin/PQQ? Or as well as?

Do you have any particular preference of NMDA agonist to try first from that list?

 

[pippocui]

Hi @Hans , I have PSSD, do you recommend me to try cistanche?

 

[Alex Jaramillo]

Do GABAergics work for sleep for you?
Have you tried progesterone vs 5a-DHP before?

Yes, progesterone works really well for me pertaining to sleep. I have never tried 5a-DHP but have some on the way right now, taking inspiration from this thread.

 

[Hans]

Yes, progesterone works really well for me pertaining to sleep. I have never tried 5a-DHP but have some on the way right now, taking inspiration from this thread.

If 3b-HSD is overactive, then you might either feel nothing from the 5a-DHP or actually slightly worse, since more of the GABA antagonist will be created.

 

[Hans]

Thanks do you think try them instead of Lapodin/PQQ? Or as well as?

Do you have any particular preference of NMDA agonist to try first from that list?

I think it's most of the time it's best to add one variable at a time and see how you respond. Or two supplements to address the same issue, such as glycine and sarcosine for example. Both will work towards the same goal. So I'd definitely try gelatin, sarcosine and tianeptine and piracetam. Piracetam can make a lot of neurotransmitters work better whereas tianeptine can promote neurological regeneration and help to enhance 5-HT1A sensitivity (since there will be less free serotonin). But then again it might be too many variables, so it's up to you which ones to try first.

 

[Jayvee]

I think it's most of the time it's best to add one variable at a time and see how you respond. Or two supplements to address the same issue, such as glycine and sarcosine for example. Both will work towards the same goal. So I'd definitely try gelatin, sarcosine and tianeptine and piracetam. Piracetam can make a lot of neurotransmitters work better whereas tianeptine can promote neurological regeneration and help to enhance 5-HT1A sensitivity (since there will be less free serotonin). But then again it might be too many variables, so it's up to you which ones to try first.

Thanks man! I’ll have a little experiment and report back with any findings.

 

[sladerunner69]

tianeptine can promote neurological regeneration

Thanks for starting this thread @Hans I don't know that tianeptine is available in the US, for those interested in trying, but I think we can still get our hands on piracetam.

Does anyone know if cortisol has a relationship with 3a-HSD? For some reason, things that affect cortisol seem to have a drastic impact on PFS guys. Just something I have noticed through the years. Licorice root, ru416, fasting etc seem to affect PFS guys in significant positive or negative ways.

Furthermore, there seems to be a strange pattern where some pfs can actually be treated by taking a low dose of a 5-ar inhibitor like licorice root or peppermint. Perhaps it lowers type 1 and icnreases type II or something to that effect. I think every case of pfs is slightly unique, and requires safe experimentation to some extent.

 

[Hans]

Thanks for starting this thread @Hans I don't know that tianeptine is available in the US, for those interested in trying, but I think we can still get our hands on piracetam.

Does anyone know if cortisol has a relationship with 3a-HSD? For some reason, things that affect cortisol seem to have a drastic impact on PFS guys. Just something I have noticed through the years. Licorice root, ru416, fasting etc seem to affect PFS guys in significant positive or negative ways.

Furthermore, there seems to be a strange pattern where some pfs can actually be treated by taking a low dose of a 5-ar inhibitor like licorice root or peppermint. Perhaps it lowers type 1 and icnreases type II or something to that effect. I think every case of pfs is slightly unique, and requires safe experimentation to some extent.

Cortisol does seem to stimulate 3a-HSD at least in adipose tissue, but it also stimulates 3b-HSD. Perhaps too much cortisol would overstimulate 3b-HSD, creating a lot of GABA antagonism.
Cortisol is also deactivated by 5-AR, so if someone has high cortisol, then low 5-AR might make it worse. Or if it's low, then high 5-AR might also make it worse.

One of the possible reasons why a low dose of 5-AR type 1 inhibitors might be helpful is because it lowers isopregnanolone production (including allopregnanolone).

 

[sladerunner69]

Cortisol does seem to stimulate 3a-HSD at least in adipose tissue, but it also stimulates 3b-HSD. Perhaps too much cortisol would overstimulate 3b-HSD, creating a lot of GABA antagonism.
Cortisol is also deactivated by 5-AR, so if someone has high cortisol, then low 5-AR might make it worse. Or if it's low, then high 5-AR might also make it worse.

One of the possible reasons why a low dose of 5-AR type 1 inhibitors might be helpful is because it lowers isopregnanolone production (including allopregnanolone).

Interesting, thanks. Perhaps this cortisol effect is yet another reason why it's difficult to improve in some areas while worsening in others.

I'm not sure I understand that last bit about 5-ar inhibition, though. Wouldn't lowering isopregnanolone lead to increased alloprenganolone, considering they seem to antagonize one another?

 

[Hans]

Interesting, thanks. Perhaps this cortisol effect is yet another reason why it's difficult to improve in some areas while worsening in others.

I'm not sure I understand that last bit about 5-ar inhibition, though. Wouldn't lowering isopregnanolone lead to increased alloprenganolone, considering they seem to antagonize one another?

Not if you block it at the level of 5AR. If you inhibit 3b-HSD, then the ratio will improve, but if you inhibit 5AR1, then the ratio will not improve, but there will only be less created.

 

[sladerunner69]

Not if you block it at the level of 5AR. If you inhibit 3b-HSD, then the ratio will improve, but if you inhibit 5AR1, then the ratio will not improve, but there will only be less created.

I see now, this makes sense. It then looks like we should find a substance which aggressively downregulates 3b-HSD. Another option would be to inhibit 5ar-1 (though it is not likely we will find information about which 5-ar inhibitors block mainly type-I or type II) and then take supplementary allopregnenelone or 5a-dhp. (Unfortunately allopregnanelone is not available at a reasonable price yet, but some is available for labratory testing at high cost).

Yet another option I had considerred may be to supplement DHT and use 5-ar inhibitors such as licorice root in an interval on/off strategy, so that the body gradually buiilds up more 5-ar enzyme.

 

[Hans]

I see now, this makes sense. It then looks like we should find a substance which aggressively downregulates 3b-HSD. Another option would be to inhibit 5ar-1 (though it is not likely we will find information about which 5-ar inhibitors block mainly type-I or type II) and then take supplementary allopregnenelone or 5a-dhp. (Unfortunately allopregnanelone is not available at a reasonable price yet, but some is available for labratory testing at high cost).

Yet another option I had considerred may be to supplement DHT and use 5-ar inhibitors such as licorice root in an interval on/off strategy, so that the body gradually buiilds up more 5-ar enzyme.

My hypothesis is to focus on lowering 3b-HSD only. If that is not done, then 5a-DHP might make your symptoms worse by converting to isopregnanolone. I had a few tell me that 5a-DHP did make them worse.
DHT and allopregnanolone would most likely have been the ideal combo.

 

[Alex Jaramillo]

If 3b-HSD is overactive, then you might either feel nothing from the 5a-DHP or actually slightly worse, since more of the GABA antagonist will be created.

I should be getting it sometime this week so i’ll keep you updated in this thread as to whether my experience with 5a-dhp is positive or negative. Progesterone has been amazing everytime i’ve taken some and i’ve tried low and high doses with nothing but positive effects. Androsterone has also always been positive. It seems pregnenolone and dhea do not produce consistently positive effects for me while prog and andro always do.

 

[Hans]

I should be getting it sometime this week so i’ll keep you updated in this thread as to whether my experience with 5a-dhp is positive or negative. Progesterone has been amazing everytime i’ve taken some and i’ve tried low and high doses with nothing but positive effects. Androsterone has also always been positive. It seems pregnenolone and dhea do not produce consistently positive effects for me while prog and andro always do.

Both progesterone and andro have potent pro-GABA effects, but they obviously have many other benefits as well. Keep us posted man.

 

[sladerunner69]

Both progesterone and andro have potent pro-GABA effects, but they obviously have many other benefits as well. Keep us posted man.

My hypothesis is to focus on lowering 3b-HSD only. If that is not done, then 5a-DHP might make your symptoms worse by converting to isopregnanolone. I had a few tell me that 5a-DHP did make them worse.
DHT and allopregnanolone would most likely have been the ideal combo.

One might be able to order both from those from a Chinese lab. I personally don't think I would try to, however.

What do you understand about cortisol's affect on 3a-hsd? I read on hackstasis that cortisol increases it significantly.

 

[Hans]

One might be able to order both from those from a Chinese lab. I personally don't think I would try to, however.

What do you understand about cortisol's affect on 3a-hsd? I read on hackstasis that cortisol increases it significantly.

Keep in mind that 3a-HSD is a bidirectional enzyme. It uses NADPH to create allopregnanolone and uses NAD to convert 3a-diol back into DHT. So an overly reduced state might lead to low DHT, but high allopregnanolone.
Also, 3b-HSD converts preg to prog, so perhaps using prog can inhibit 3b-HSD through a negative feedback loop.

Too much preg-S could also cause problems by inhibiting GABA. Some people do terribly bad with supplemental preg, even in small doses.

Cortisol seems to inhibit 3b-HSD and lower progesterone synthesis from preg, but that can lead to elevated preg-S and DHEA-S, both of which are GABA antagonists.
Stress stimulates the creation of allopregnanolone, so it's possible that cortisol stimulates 3a-HSD.

 

[sladerunner69]

Keep in mind that 3a-HSD is a bidirectional enzyme. It uses NADPH to create allopregnanolone and uses NAD to convert 3a-diol back into DHT. So an overly reduced state might lead to low DHT, but high allopregnanolone.
Also, 3b-HSD converts preg to prog, so perhaps using prog can inhibit 3b-HSD through a negative feedback loop.

Too much preg-S could also cause problems by inhibiting GABA. Some people do terribly bad with supplemental preg, even in small doses.

Cortisol seems to inhibit 3b-HSD and lower progesterone synthesis from preg, but that can lead to elevated preg-S and DHEA-S, both of which are GABA antagonists.
Stress stimulates the creation of allopregnanolone, so it's possible that cortisol stimulates 3a-HSD.

This all makes good sense to me, as I feel calmer and more focussed mentally when I fast (increased cortisol) but not for too long. After a half day of fasting I begin to get irritable and angry.

I tried some plain old DHEA the other day for the first time in several months and it gave me an incredible boost in energy, like I could handle anything.

When I take progesterone I become more relaxed but also tired and almost too uncaring about things. When I don't take any I have more energy but am more irritable. Maybe the combination of progesterone and dhea is best, along with some morning fasting to keep cortisol levels a bit higher. I have long since been concerned that constantly eating fruit and sugars might be keeping my cortisol too low. I know some people do very well on IF, and older people will feel great after getting hydrocortisone injections.

 

[Jayvee]

This all makes good sense to me, as I feel calmer and more focussed mentally when I fast (increased cortisol) but not for too long. After a half day of fasting I begin to get irritable and angry.

I tried some plain old DHEA the other day for the first time in several months and it gave me an incredible boost in energy, like I could handle anything.

When I take progesterone I become more relaxed but also tired and almost too uncaring about things. When I don't take any I have more energy but am more irritable. Maybe the combination of progesterone and dhea is best, along with some morning fasting to keep cortisol levels a bit higher. I have long since been concerned that constantly eating fruit and sugars might be keeping my cortisol too low. I know some people do very well on IF, and older people will feel great after getting hydrocortisone injections.

Hey man what doses of progesterone have you tried? I still haven’t tried progesterone and no idea how to dose for PFS (if different).

 

[Hans]

This all makes good sense to me, as I feel calmer and more focussed mentally when I fast (increased cortisol) but not for too long. After a half day of fasting I begin to get irritable and angry.

I tried some plain old DHEA the other day for the first time in several months and it gave me an incredible boost in energy, like I could handle anything.

When I take progesterone I become more relaxed but also tired and almost too uncaring about things. When I don't take any I have more energy but am more irritable. Maybe the combination of progesterone and dhea is best, along with some morning fasting to keep cortisol levels a bit higher. I have long since been concerned that constantly eating fruit and sugars might be keeping my cortisol too low. I know some people do very well on IF, and older people will feel great after getting hydrocortisone injections.

Have you tried cortinon?

 

[llian]

If someone has too much isopregnanolone, then lowering type I might actually be helpful as it will lower isopregnanolone, but also allopregnanolone. Someone has speculated the people with PSSD might have too much allopregnanolone, so perhaps it's worth a shot trying cistanche for that as well.

Hey man if Cistanche can lower allopregnanolone and someone wants this herb benefits without messing hormones up, it would be wise to take
Kami-shoyo-san with it, which seem to raise allopregnanolone ? Both seem to go well together wdyt btw i dont suffer from PSSD, i just one the mental benefits from this herb.