• Due to excessive bot signups along with nefarious actors we are limiting forum registration. Keep checking back for the register link to appear. Please do not send emails or have someone post to the forum asking for a signup link. Until the current climate changes we do not see a change of this policy. To join the forum you must have a compelling reason. Letting us know what skills/knowledge you will bring to the community along with the intent of your stay here will help in getting you approved.

Pregnenolone Is A Potent Aldosterone Antagonist (antimineralocorticoid)

haidut

Member
Joined
Mar 18, 2013
Messages
18,409
Location
USA / Europe
Ray has written a number of articles on the hypertension, heart and kidney failure, eclampsia, and CVD in which he describes the central role of aldosterone in the pathogenesis of these conditions. Aldosterone antagonists (antimineralocorticoids - e.g. spironolactone, itself a pregnenolone derivative) are mainstream therapy for heart failure and prevention of both first and subsequent heart attacks. I posted a thread some time ago showing that cyproheptadine can reliably lower aldosterone. This study shows that pregnenolone (just like progesterone) is a potent aldosterone antagonist in low nanomolar concentrations (IC50: 72nM/L).

Occurrence of androgens in sewage treatment plants influents is associated with antagonist activities on other steroid receptors. - PubMed - NCBI
Occurrence of androgens in sewage treatment plants influents is associated with antagonist activities on other steroid receptors

"...Highlights ► Steroid receptor profiling of STPs extracts using in vitro steroid receptor bioassays. ► Presence of agonist ER and AR, and antagonist GR, PR and MR activities in samples. ► Analysis of the STPs activities due to human steroids. ► AR, anti-GR and PR activities were not due to known human androgens. ► The steroid precursor pregnenolone is a potent anti-mineralocorticoid."

"...Interestingly, using LC MS/MS (Liquid chromatography coupled to tandem mass spectrometry), we detected the presence of pregnenolone at high concentrations in the S2 and S4 samples. Using our bioluminescent reporter cells, pregnenolone was identified as a potent MR antagonist with a faint antagonist activity on PR and AR (Fig. 4B and Table 4 for the IC50) and a weak agonist activity on ERa (Fig. S3). Chemical analysis indicated that pregnenolone significantly contributed to the Bio-Spiro-Eqs (54.9 and 7.3% see Table 3). Altogether, these results identify pregnenolone as a novel EDCs acting as an important contributor to the detected antimineralocorticoid activity."
 
Last edited:

haidut

Member
Thread starter
Joined
Mar 18, 2013
Messages
18,409
Location
USA / Europe

dfspcc20

Member
Joined
Dec 9, 2015
Messages
590
My mom was "diagnosed" by her idiot doctors with Secondary Hyperaldosteronism. They didn't even consider it could have been caused by the super low-sodium diet they recommended for her many years prior for her Ménière's disease, along with potassium supplements. I've been trying unsuccessfully ever since to get her to add more salt again, while watching her basically fall apart and develop many more issues.

Maybe I'll be able to convince her to try pregnenolone, progesterone, and/or cyproheptadine for the Secondary Hyperaldosteronism, rather than what ever else they're giving her for it. I doubt it though, unless the doctor says it. Those would likely help with the Ménière's as well, according to previous Peat quotes.
 

Drareg

Member
Joined
Feb 18, 2016
Messages
3,974
Ray has written a number of articles on the hypertension, heart and kidney failure, eclampsia, and CVD in which he describes the central role of aldosterone in the pathogenesis of these conditions. Aldosterone antagonists (antimineralocorticoid) are mainstream therapy for heart failure and prevention of both first and subsequent heart attacks. I posted a thread some time ago showing that cyproheptadine can reliably lower aldosterone. This study shows that pregnenolone (just like progesterone) is a potent aldosterone antagonist in low nanomolar concentrations (IC50: 72nM/L).

Occurrence of androgens in sewage treatment plants influents is associated with antagonist activities on other steroid receptors. - PubMed - NCBI
Occurrence of androgens in sewage treatment plants influents is associated with antagonist activities on other steroid receptors

"...Highlights ► Steroid receptor profiling of STPs extracts using in vitro steroid receptor bioassays. ► Presence of agonist ER and AR, and antagonist GR, PR and MR activities in samples. ► Analysis of the STPs activities due to human steroids. ► AR, anti-GR and PR activities were not due to known human androgens. ► The steroid precursor pregnenolone is a potent anti-mineralocorticoid."

"...Interestingly, using LC MS/MS (Liquid chromatography coupled to tandem mass spectrometry), we detected the presence of pregnenolone at high concentrations in the S2 and S4 samples. Using our bioluminescent reporter cells, pregnenolone was identified as a potent MR antagonist with a faint antagonist activity on PR and AR (Fig. 4B and Table 4 for the IC50) and a weak agonist activity on ERa (Fig. S3). Chemical analysis indicated that pregnenolone significantly contributed to the Bio-Spiro-Eqs (54.9 and 7.3% see Table 3). Altogether, these results identify pregnenolone as a novel EDCs acting as an important contributor to the detected antimineralocorticoid activity."

When you consider the actions of HSD11B2, do you think anything that inactivates/lowers cortisol will leave aldosterone unopposed in some cases? I understand they have a sensitive ratio where cortisol outcompetes aldosterone.

Niacinamide,creatine and aspirin can cause slight water retention,puffiness in some cases,the creatine complaints are well known,it seems using these substances without checking the aldosterone could be causing it?
 

haidut

Member
Thread starter
Joined
Mar 18, 2013
Messages
18,409
Location
USA / Europe
When you consider the actions of HSD11B2, do you think anything that inactivates/lowers cortisol will leave aldosterone unopposed in some cases? I understand they have a sensitive ratio where cortisol outcompetes aldosterone.

Niacinamide,creatine and aspirin can cause slight water retention,puffiness in some cases,the creatine complaints are well known,it seems using these substances without checking the aldosterone could be causing it?

It is actually the elevated cortisol that can outcompete aldosterone for binding to the MR receptor and this is what causes the water retention, puffiness and hypertension in high cortisol states. Aldosterone is primarily driven by sodium levels in the blood so the control mechanism is (usually) not dependent on cortisol levels. What aldosterone can cause is fibrosis if it is elevated chronically. I think aldosterone is also driven by serotonin, which is not surprising since serotonin is de-activated in a sodium-dependent fashion (i.e. the SERT protein), so it's down to sodium again.
 

yerrag

Member
Joined
Mar 29, 2016
Messages
9,145
Location
Manila
This study shows that pregnenolone (just like progesterone) is a potent aldosterone antagonist in low nanomolar concentrations (IC50: 72nM/L).
I tried to get the amount from this but realize this isn't a metric I can work with since it's given not in terms of molarity, but in terms of concentration. It comes out as .02 mg/L. Assuming there's 5 liters of blood in our body, this just comes out as 1mg dosage. Doesn't sound right.

If I weigh around 70 kg, and 65% of it is water, then the water content is 45 kg or liters. This comes out to 45mg of pregnenolone. Is this correct?
 

haidut

Member
Thread starter
Joined
Mar 18, 2013
Messages
18,409
Location
USA / Europe
I tried to get the amount from this but realize this isn't a metric I can work with since it's given not in terms of molarity, but in terms of concentration. It comes out as .02 mg/L. Assuming there's 5 liters of blood in our body, this just comes out as 1mg dosage. Doesn't sound right.

If I weigh around 70 kg, and 65% of it is water, then the water content is 45 kg or liters. This comes out to 45mg of pregnenolone. Is this correct?

There is something called volume of distribution (VoD) for chemicals and it basically calculates what volume inside your body a chemical is distributed across. So, it is not just blood but all tissues that can take up a chemical. The maximum VoD would be entirely hollow body encased in the skin. The minimum VoD would be zero - the body refuses to uptake ANY amount of the chemical. The VoD tends to be different for every chemical. Without going into too much details, the volume of distribution of pregnenolone is about 1.3 L / kg.
https://joe.bioscientifica.com/abstract/journals/joe/39/3/joe_39_3_010.xml

That means the volume of distribution for a 100kg person would be 130 L. In the case of pregnenolone for aldosterone antagonism that means 0.02mg / L * 130 L (for a 100kg person) = 2.6mg (assuming 100% absorption after oral administration). So, sounds about right considering 72 nM/L concentration is really not much and considered quite potent effect for a chemical. In general, anything acting on a receptor in nanomolar concentrations is considered potent.
As far as pregnenolone for aldosterone antagonism, I personally find slightly higher doses in the 5mg-10mg to work better, possibly because not all of it gets absorbed when ingested.
 

yerrag

Member
Joined
Mar 29, 2016
Messages
9,145
Location
Manila
I tried to get the amount from this but realize this isn't a metric I can work with since it's given not in terms of molarity, but in terms of concentration. It comes out as .02 mg/L. Assuming there's 5 liters of blood in our body, this just comes out as 1mg dosage. Doesn't sound right.

If I weigh around 70 kg, and 65% of it is water, then the water content is 45 kg or liters. This comes out to 45mg of pregnenolone. Is this correct?
Wrong calculation : 1 mg should actually be 0.1 mg; 45 mg should be .45 mg. More far off.
There is something called volume of distribution (VoD) for chemicals and it basically calculates what volume inside your body a chemical is distributed across. So, it is not just blood but all tissues that can take up a chemical. The maximum VoD would be entirely hollow body encased in the skin. The minimum VoD would be zero - the body refuses to uptake ANY amount of the chemical. The VoD tends to be different for every chemical. Without going into too much details, the volume of distribution of pregnenolone is about 1.3 L / kg.
https://joe.bioscientifica.com/abstract/journals/joe/39/3/joe_39_3_010.xml

That means the volume of distribution for a 100kg person would be 130 L. In the case of pregnenolone for aldosterone antagonism that means 0.02mg / L * 130 L (for a 100kg person) = 2.6mg (assuming 100% absorption after oral administration). So, sounds about right considering 72 nM/L concentration is really not much and considered quite potent effect for a chemical. In general, anything acting on a receptor in nanomolar concentrations is considered potent.
As far as pregnenolone for aldosterone antagonism, I personally find slightly higher doses in the 5mg-10mg to work better, possibly because not all of it gets absorbed when ingested.
Thanks for the explanation haidut. So, I should be about right using 10 mg of pregnenolone from Pansterone (8 drops, although there's as much DHEA there).
 

LeeLemonoil

Member
Joined
Sep 24, 2016
Messages
2,756

Similar threads

Top