Recovering Steroidogenesis Inhibited By Alcohol And Drugs

[haidut]

As many of you know, drugs like Finasteride are really bad not only because they cause a variety of CNS effects as a result of inhibiting 5-AR, but also because they systemically inhibit the entire steroid synthesis cascade. Toxins and alcohol do the same and currently there is no approved medical treatment for the chemical castration induced by these poisons. Some studies have suggested supplementing with pregnenolone and DHEA may help but one must also make sure that the steroid synthesis enzymes are also working. Deficiencies in vitamin A can make steroid supplementation ineffective. Also, pretty much all of the steroid synthesis enzymes upstream are NAD-dependent. This means supplementing niacinamide may also have to be considered. This excerpt shows that while neither pregnenolone nor NAD on their own were effective, supplementing both was effective in restoring steroid synthesis compromised by alcohol. So, for PFS sufferers, the protocol may have to combine pregnenolone/DHEA with some niacinamide (abd maybe vitamin A) for full effectiveness.

https://tahomaclinic.com/Private/Articles1/Testosterone/Widenius%201987%20-%20Inhibition%20of%20testosterone%20biosynthesis%20by%20ethanol.pdf

Ethanol-induced reductions in testicular steroidogenesis: major differences between in vitro and in vitro approaches. - PubMed - NCBI
"...Under in vitro conditions, we observed that ethanol selectively inhibited the conversion of androstenedione to testosterone, but that it had a much more general effect under in vivo conditions. In addition, in agreement with other studies, NAD+ overcame ethanol's effects on testicular steroidogenesis in vitro, but only when labeled or unlabeled pregnenolone was added. In the absence of added pregnenolone, NAD+ was not effective in preventing ethanol's effects. Our results, thus, indicate that the differences which currently exist in the literature may be explained by the indiscriminate usage of in vivo and in vitro techniques."

 

[Hugh Johnson]

Usually these studies use something like 30% of calories from ethanol. Which is kind of like doing caffeine studies with the human equivalent of 10g a day. Pretty easy to prove almost anything kills you if you add enough of it.

 

[Drareg]

As many of you know, drugs like Finasteride are really bad not only because they cause a variety of CNS effects as a result of inhibiting 5-AR, but also because they systemically inhibit the entire steroid synthesis cascade. Toxins and alcohol do the same and currently there is no approved medical treatment for the chemical castration induced by these poisons. Some studies have suggested supplementing with pregnenolone and DHEA may help but one must also make sure that the steroid synthesis enzymes are also working. Deficiencies in vitamin A can make steroid supplementation ineffective. Also, pretty much all of the steroid synthesis enzymes upstream are NAD-dependent. This means supplementing niacinamide may also have to be considered. This excerpt shows that while neither pregnenolone nor NAD on their own were effective, supplementing both was effective in restoring steroid synthesis compromised by alcohol. So, for PFS sufferers, the protocol may have to combine pregnenolone/DHEA with some niacinamide (abd maybe vitamin A) for full effectiveness.

Ethanol-induced reductions in testicular steroidogenesis: major differences between in vitro and in vitro approaches. - PubMed - NCBI
"...Under in vitro conditions, we observed that ethanol selectively inhibited the conversion of androstenedione to testosterone, but that it had a much more general effect under in vivo conditions. In addition, in agreement with other studies, NAD+ overcame ethanol's effects on testicular steroidogenesis in vitro, but only when labeled or unlabeled pregnenolone was added. In the absence of added pregnenolone, NAD+ was not effective in preventing ethanol's effects. Our results, thus, indicate that the differences which currently exist in the literature may be explained by the indiscriminate usage of in vivo and in vitro techniques."

Great find.
What kind of dosages do you think would be reasonable Per day ?

 

[haidut]

Great find.
What kind of dosages do you think would be reasonable Per day ?

They used physiological doses of pregnenolone, so even 10mg - 30mg pregnenolone daily should suffice, combined with the usual Peat dose of 100mg niacinamide taken 2-3 times a day. I would throw in 5mg DHEA as well if there is no observable effects within a week.

 

[Jsaute21]

@haidut just curious do you ever drink? And if you do decide to occasionally partake, are these the precautions you take?

 

[haidut]

@haidut just curious do you ever drink? And if you do decide to occasionally partake, are these the precautions you take?

I do sometimes, but have very little free time so probably once or twice a week 1-2 beers at a time. I take vitamin B6, B3 and B1 before drinking but with so little alcohol there is probably no need for precautions. For heavy drinking, I would do take these though. Maybe some methylene blue after drinking to oxidize the ethanol more quickly. Sugar and especially fructose helps a lot too.

 

[Jsaute21]

I do sometimes, but have very little free time so probably once or twice a week 1-2 beers at a time. I take vitamin B6, B3 and B1 before drinking but with so little alcohol there is probably no need for precautions. For heavy drinking, I would do take these though. Maybe some methylene blue after drinking to oxidize the ethanol more quickly. Sugar and especially fructose helps a lot too.

Thanks man. Yeah, especially in this hot weather, a cold beer is too smooth to pass up.

 

[sladerunner69]

Yes I was attempting to increase GABA with alcohol because I am a long time finasteride victim, and it seems to help briefly but then my libido crashes and I become lethargic and crankly for the rest of the day, even from just one or two vodka&cokes. Small amounts of alcohol does help my mental side effects greatly for a few hours, although Im sure anyone could attest to alcohol making them feel better. With the terrible lethargy and apathy hangovers though, I figured the alcohol was causing some serious inhibitions to androgens and pregnenelone so these finding make sense.

 

[haidut]

Yes I was attempting to increase GABA with alcohol because I am a long time finasteride victim, and it seems to help briefly but then my libido crashes and I become lethargic and crankly for the rest of the day, even from just one or two vodka&cokes. Small amounts of alcohol does help my mental side effects greatly for a few hours, although Im sure anyone could attest to alcohol making them feel better. With the terrible lethargy and apathy hangovers though, I figured the alcohol was causing some serious inhibitions to androgens and pregnenelone so these finding make sense.

The apathy is from dopamine downregulation and serotonin agonism (ethanol is 5-HT3 agonist) after drinking and the lethargy is from NAD depletion. So, something like a small dose DHEA (which lowers prolactin) with a decent protein meal and some niacinamide should reverse this. And the B1, B3, and B6 vitamins I mentioned earlier can possibly prevent the hangover and apathy from even happening.

 

[Jsaute21]

The apathy is from dopamine downregulation and serotonin agonism (ethanol is 5-HT3 agonist) after drinking and the lethargy is from NAD depletion. So, something like a small dose DHEA (which lowers prolactin) with a decent protein meal and some niacinamide should reverse this. And the B1, B3, and B6 vitamins I mentioned earlier can possibly prevent the hangover and apathy from even happening.

I tried your experiment last night @haidut , as i was out and had 3-4 beers with friends. (Coors light so not too detrimental.)

I noticed a couple of things, eating a healthy dinner (shrimp, white rice cooked in butter with a coke) prior was a great help. I also did not possess the desire to get inebriated what so ever. I have always been far from an alcoholic, especially compared to many of my buddies, but i think when one is in somewhat of a stress hormone/estrogenic state, they exhibit alcoholic behavior, and binge drink. I also took MB, energin, and some pine pollen. I woke up with a headache, which i think was more related to actually speeding my metabolism up with those supps than it was the booze, as 3-4 beers would never give me a hangover. However, after my morning coffee i feel completely back to normal and pretty good.

This is all highly individual stuff, but as usual very helpful studies and experiments from the man, the myth, the legend @haidut.

 

[A.R]

The apathy is from dopamine downregulation and serotonin agonism (ethanol is 5-HT3 agonist) after drinking and the lethargy is from NAD depletion. So, something like a small dose DHEA (which lowers prolactin) with a decent protein meal and some niacinamide should reverse this. And the B1, B3, and B6 vitamins I mentioned earlier can possibly prevent the hangover and apathy from even happening.

Could you please elaborate through which specific mechanisms DHEA lowers Prolactin

Thank You

 

[haidut]

Could you please elaborate through which specific mechanisms DHEA lowers Prolactin

Thank You

I don't know for sure, but a few studies showed DHEA inhibiting TPH and anything that lower TPH will lower serotonin and tend to increase dopamine.

 

[TubZy]

Probably why niacinamide PLUS caffeine is so much more superior for PFS people due to restoring NAD levels as cofactors for steroid synthesis. When I take caffeine with 500mg or more of niacinamide there is a big difference compared to just caffeine alone.

But it seems it can work in many other situations I.e. preg + niacinamide too..

Never tried caffeine + retinol either

 

[EIRE24]

Probably why niacinamide PLUS caffeine is so much more superior for PFS people due to restoring NAD levels as cofactors for steroid synthesis. When I take caffeine with 500mg or more of niacinamide there is a big difference compared to just caffeine alone.

But it seems it can work in many other situations I.e. preg + niacinamide too..

Never tried caffeine + retinol either

How come niacinamide can slow down fat loss but speeds up metabolism? I know that it inhibits FFA from being burned but in that situation how would someone lose weight if they wanted to take niacinamide

 

[NathanK]

The apathy is from dopamine downregulation and serotonin agonism (ethanol is 5-HT3 agonist) after drinking and the lethargy is from NAD depletion. So, something like a small dose DHEA (which lowers prolactin) with a decent protein meal and some niacinamide should reverse this. And the B1, B3, and B6 vitamins I mentioned earlier can possibly prevent the hangover and apathy from even happening.

Sounds like a new hangover product


Btw, they sell caps of DHEA & Preg out there (along with your product). The studies on this combination appear to be popular. I experimented with one last year that had 10mg preg and 5DHEA which was okay, but didnt seem as effective as others.

 

[jacknap]

Probably why niacinamide PLUS caffeine is so much more superior for PFS people due to restoring NAD levels as cofactors for steroid synthesis. When I take caffeine with 500mg or more of niacinamide there is a big difference compared to just caffeine alone.

But it seems it can work in many other situations I.e. preg + niacinamide too..

Never tried caffeine + retinol either

can't wait to get my proper niacinamide. I was using niacin like a dope. after going off caffeine for a month or so and using it again, definitely felt amazing on it.

when u talk of this combo though, does it work consistently or do you develop tolerance? or does it kickstart our neurosteroids in the right way that the body takes over after? I want to a cure not a crutch. safe crutches are always welcome too though.

 

[Xemnoraq]

@haidut hey Georgi, in my opinion i think alot of these people could have low steroids due to vitamin deficiencies as well, you mentioned thiamine as a huge factor of deficiency for alcoholics, im assuming part of the recovery is getting your steroids to run on proper nutrition rather than stimulants,

As far as i understand alot of drugs act like thyroid hormone even caffeine for example, but these can never replace proper nutrition so if done excessively causes burnout,

In my own personal experience i have found thiamine to make the biggest difference for me,

I smoked tobacco excessively this year as an experiment to see if it had similar beneficial properties such as caffeine, however even before that i would drink coffee excessively without backing it up with proper nutrition,

Some of these habits of using substance usualy involve people skipping meals and replacing nutrition with substances so then when theres no substance to stimulate metabolism plus deficiencies you end up with a major burnout,

This was my case, excessive caffeine and tobacco combined with undereating, lots of white sugar without sufficient vitamins so im under the assumption i was severely deficient in thiamine,

Caffeine blocks thiamine absorbtion, white sugar and extra carbs increase the need for thiamine and other b-vitamins, and i recall reading tobacco has a negative effect on b1 status,

So with that being said, alot of people when they quit these substances seem to be in more poor health when they were using them ive noticed? And i think this is because when you remove the stimulant, your far more exposed to the cascade of stress hormones, this is commonly seen, and its even been known that withdrawal itself is actually dangerous! If not nutritionally supported and can sometimes aparently result in increased mortality,

It seems to me withdrawal really needs to be supported in every way possible nutritionally maybe with more then even pregnenalone and niacinamide, itd be interesting to discuss the effect of vitamin deficiencies in the severity of withdrawal,

In my case i felt like a complete zombie quitting tobacco, taking 300mg b1 takes away almost all of my symptoms,

I believe someone on the forum shared a thread with a study demonstrating b1 deficiency results in something like 50% higher serotonin levels and im just paraphrasing so forgive me if the quotes arent 100% correct,

But it makes sense the body would want to slow its metabolism with serotonin in the case of a deficiency to conserve and go longer on less, the inefficient metabolism,

So in situations like this would you say it would make more sense to correct the deficiency rather than using serotonin antagonists? Fix the reason the serotonin is high? And maybe use serotonin antagonists if nutrition is good at the time?

Curious to know your opinions on this.

 

[Xemnoraq]

@haidut by the way great post! Id also be curious to know if your aware of any post quitting smoking effects on steroids, it seems everyone who quits smoking their health goes to complete ***t after,

My assumption of this is because there are MAO inhibitors in tobacco acting like SSRI's,

So with that being said if you are exposed to an SSRI nicotine having a pro dopamine temporary anti-serotonin effect may largely protect against the MAO inhibitors, however when you discontinue the nicotine, its possible then you may be fully exposed to the after effects of the MAO inhibitors, along with maybe any other accumulated toxins,

Do you have any interesting information or knowledge in how the MAO inhibitors in tobacco may relate to its SSRI effect?

I personally believe the MAO inhibitors present may be driving the negative feedback from tobacco abstinence, and the heavy additions that follow.