Ideas On Pregnenalone Supp

[trevorbayliss]

Hello I am a new member and thought i would get some opinions on my use of pregnenalone.

I am hypothyroid and take 150 T4. All is pretty good now with my health, but i found pregnenalone to really help last summer when i first started to use it.

After a few weeks using 50mcg per day i found i went off slightly health wise. Any way i have now started to use pregnenalone very sparingly as quite often when i use it i become tired.

So i tried it again today after 10 days off it and just 50mcg has made me very tired again. However, i am sure in the next day or two i will feel really good.

So can anyone say why the pregnenalone is having this negative effect on me. I have been reading threads on here and think i now need to use a much smaller dose if i am to use it at all. Say maybe a 25mcg dose every 10 or so days. I suppose i will have to work that one out. I am 39 y/o, male.

I thought pregnenalone just replaces what is missing automatically and you cannot over use it, but that is not the case i am finding.

Any input will be appreciated as i have found pregnenalone to be the one thing (apart from thyroid meds) to really help improve my health.

 

[Blossom]

It could be that you don't need much or it could be fillers in the brand you take. It seems like self experimentation is the best approach. I noticed better results from the powder form compared to the capsules personally. Some people seem more sensitive to the additives than others. I had that reaction once in my earlier experimental phase when I took 670mg. It pretty much knocked me out, or at least I attributed my reaction that day to the very high dose since it was the only thing different I had done. I also take Progest-e so maybe I had a bit too much progesterone in my system with that combination. It seems younger people may not normally need as much, but of course everything in context. Best of luck, the good thing is that it is safe at any dose according to RP.

 

[trevorbayliss]

ok thanks. I feel much better this evening. So basically my body has taken 12h's to get over the 50mcg amount i took.

Reading the info on here has made me realise i can just open up my capsules and divide them up. I will see how 25mcgs goes in a few days time.

 

[j.]

What brand are you using?

 

[trevorbayliss]

Eurovital in the UK. Used to be biovea but they had a rebrand. 50mcg tablets

 

[j.]

Other Ingredients: Rice flour, gelatin, magnesium stearate, silicon dioxide.

I can't consume anything that has silica without getting bad reactions.

 

[Suikerbuik]

Saw a sort of hormone guide lately - was posted on this forum. It was all about raising metabolism with thyroid and in case low cortisol, pregnenolone.

if I recall right, it was stated that pregnenolone at higher doses might raise cortisol and thus suppress ACTH (And seemingly also CRH [1]). This lower ACTH could make you tired and yawning, as there' a temporary reduction in own cortisol production. ACTH does induce pregnenolone production, by activating (multiple) enzymes.

ACTH binds to one or more specific receptors in the adrenocortical cell membrane (represented by A and B in the figure below) which has the effect of activating adenylate cyclase (ACase). The cytosolic concentration of adenosine 3,5-cyclic monophosphate (cAMP) increases, in turn a) activating cholesterol ester (CE) hydrolase, which catalyses the conversion of cholesterol ester into free cholesterol, and b) facilitating the transfer of cholesterol within the mitochondrion to a site accessible to the scc enzyme. Furthermore, low density lipoprotein receptor-mediated uptake of plasma cholesterol together with cytosolic cholesterol synthesis provide substrate for steroid synthesis, and both these processes can be controlled by an intracellular pool of cholesterol.[1]

I can't find anything in the literature about pregnenolone being able to supress ACTH directly, but if ACTH only induces it's effect on pregnenolone synthesis and not on expression/activating enzymes that control the synthesis of cortisol. Pregnenolone can and will raise cortisol levels dose dependently, thus leading to lower ACTH. This probably is what Ray means with the possibility of pregnenolone being able to raise or reduce cortisol.

Ray stated some that Thyroid is the biggest factor in pregnolone production (in the mitochondria), so as you say my health has improved your own production may be better and so you don't need any more.

I also feel I need less and less to overtime (in few weeks only). Anyway when it's about hormones it's so personal.. I really think very little is known about how these substances interact with our genetics, which also varies individually. Pregnenolone doesn't lead straight to cortisol, so IF it does, we don't know how much. And since it's likely there's also a dose depent concentration gradiënt between the bloodstream and intracellular fluid and probably also between the intracellular fluid and mitochondria. There's no known dose for this to happen (would differ in each person too, again).

1. A mechanistic model of ACTH-stimulated cortisol secretion

 

[MyUsernameHere]

Today I received my LEF 100 mg Pregnenolone, took a whole capsule and felt nothing. Will see after a few days, but looks like it's gonna be disappointing (just like most other hormones I tried so far).

 

[j.]

I think pregnenolone takes a while to be converted to the final hormone (progesterone, testosterone, etc.).

 

[trevorbayliss]

Thanks for info Sulkerbulk. Interesting

 

[Blossom]

I definitely benefit from it. When I stopped it for about a week my feet were cold as ice. I'm middle aged though so it probably is helping me make DHEA if I had to guess.

 

[Suikerbuik]

The latest step in cortisol synthesis (converting 11-deoxycortisol into cortisol) is carried out by steroid 11-beta-hydroxylase, which is indeed (partly?) regulated by ACTH as more steps in the synthesis of steroid hormones are[1].

We studied the kinetics of corticotropin (ACTH) induction of mitochondrial cytochromes P450scc and P450,11 and their electron transport proteins, adrenodoxin and adrenodoxin reductase, in bovine adrenal cortex cells in primary culture. The mRNA levels of these enzymes increase and reach a peak within 3-12 h after ACTH addition. The protein levels of adrenodoxin reductase and P450scc show an increase only nearly 24 h after ACTH addition.

[1]Mechanism of Corticotropin and CAMP Induction of Mitochondrial Cytochrome P450 System Enzymes in Adrenal Cortex Cells*

ps: P450scc is the enzyme that convert cholesterol into pregnenolone.

"... In health, enough pregnenolone and progesterone are produced to inhibit the stress systems, for example by inhibiting the release of ACTH. When something prevents the formation of pregnenolone and progesterone, rising ACTH will increase its production as conditions permit, but if something, such as thyroid hormone, is lacking, the ACTH will increase cortisol, often with DHEA and the androgens increasing too, if resources permit; sometimes the stressed system is able to sustain only cortisol and aldosterone production, and that leads to degenerative problems." - Ray Peat

Found this latest quote of Ray Peat at Danny Roddy's site I don't know in which article of Dr. Peat you can read more.

IF pregnenolone leads to lower ACTH levels then this may indeed have a systemic effect, which could really affect things like our own cortisol production but it that effects occurs so fast? I don't find that really likely, unless ACTH itself has more activitating/devastating properties.

 

[docall18]

In many men pregnenolone raises estrogen.

I was under range in preg and started supplementing. Felt great initially but soon developed high estrogen symptoms. Taking Indolplex DIM & zinc initially, and now arimidex keeps the estrogen down. Its not ideal to having to stack supplements but without preg i feel bad, now with 150mg MLM preg & arimidex i feel great. So easy choice.