Pregnenolone Stops Bile Production? (A Hint To Constipation?)

[youngsinatra]

I am curious about the effects of supplemental pregnolone on the liver/gallbladder and biliary secretion/excretion, because I noticed signs of poor bile output after a week of using it, esp. poorer fat absorption (slight malabsorption) and constipation. Because of my long-term struggle with a sluggish liver, this effect is ever-so-more-clearly if a substance causes it.

The effect reverses after a few days of stopping pregnenolone. (I was taking 50mg every other day)

I unfortunately only found this one paper in rats.

Modulation of the stimulatory effect of pregnenolone-16 alpha-carbonitrile on biliary cholesterol output in the rat by manipulation of the rate of hepatic cholesterol synthesis - PubMed

In female rats fed a plain ground diet containing pregnenolone-16 alpha-carbonitrile, biliary cholesterol output increased twofold, whereas bile acid and phospholipid output either remained unchanged or decreased slightly. There was a 32% increase in liver weight, a 3.5-fold increase in...

pubmed.ncbi.nlm.nih.gov

„In female rats fed a plain ground diet containing pregnenolone-16 alpha-carbonitrile, biliary cholesterol output increased twofold, whereas bile acid and phospholipid output either remained unchanged or decreased slightly. There was a 32% increase in liver weight, a 3.5-fold increase in cholesteryl esters, and a 45% decrease in the rate of hepatic sterol synthesis. When pregnenolone-16 alpha-carbonitrile was fed with AOMA, an agent that blocks cholesterol absorption, there was less of an increase in cholesteryl esters, the inhibitory effect of pregnenolone-16 alpha-carbonitrile on hepatic sterol synthesis was abolished, and biliary cholesterol output was increased to an even greater extent. In contrast, when pregnenolone-16 alpha-carbonitrile was fed together with cholesterol, there was a 14-fold increase in the level of cholesteryl esters, an 85% decrease in the rate of hepatic sterol synthesis, and a marked reduction in biliary cholesterol output. The increase in biliary cholesterol saturation produced by either pregnenolone-16 alpha-carbonitrile alone or pregnenolone-16 alpha-carbonitrile with AOMA occurred with little or no change in plasma cholesterol levels and bile acid pool size. Because biliary cholesterol saturation in rats given pregnenolone-16 alpha-carbonitrile appears to correlate with the rate of hepatic cholesterol synthesis, the drug likely mediates its effect on biliary lipid composition at an intrahepatic level and may provide an important model for determining how overproduction of cholesterol by the body results in excessive transport of cholesterol into bile.“

It does seem to negatively impact bile production, unfortunately.

Does anyone have experienced the same?

 

[miquelangeles]

I experimented with the same dose last year and I also noticed this effect.
But it's more likely to be caused by an increase in progesterone, as I got it when trying prog on its own too and there are quite a few studies showing that prog inhibits motility as well as anecdotal reports. Same with herbs like Asparagus racemosus (Shatavari) and Guggul (when taken alone) both of them are progestogens. With doses of 2.5-7.5 mg of preg this didn't happen.

 

[youngsinatra]

I experimented with the same dose last year and I also noticed this effect.
But it's more likely to be caused by an increase in progesterone, as I got it when trying prog on its own too and there are quite a few studies showing that prog inhibits motility as well as anecdotal reports. Same with herbs like Asparagus racemosus (Shatavari) and Guggul (when taken alone) both of them are progestogens. With doses of 2.5-7.5 mg of preg this didn't happen.

Interesting. I have seen studies suggesting that high progesterone levels can cause the well-known „cholestasis of pregnancy“

 

[Mauritio]

If anything pregnane steroids should help with gallbladder issues ,since they acitvate the PXR , which has been known to do that. Pregnenolone and progesterone are both ligands on PXR not sure about their affinity for it.

"Thus, PXR serves as a physiological sensor of lithocholic acid and perhaps other bile acids and coordinately regulates genes involved in their detoxification. Interestingly, both the antibiotic rifampicin and the herbal antidepressant St. John's wort activate PXR and have anticholestatic properties, which suggests that more potent, selective PXR agonists may be useful in the treatment of biliary cholestasis or other diseases characterized by the accumulation of bile acids or other toxins in the liver."
- Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor - PubMed

- Pregnane X receptor - Wikipedia

- Activation of pregnane X receptor by pregnenolone 16 α-carbonitrile prevents high-fat diet-induced obesity in AKR/J mice - PubMed

 

[youngsinatra]

If anything pregnane steroids should help with gallbladder issues ,since they acitvate the PXR , which has been known to do that. Pregnenolone and progesterone are both ligands on PXR not sure about their affinity for it.

"Thus, PXR serves as a physiological sensor of lithocholic acid and perhaps other bile acids and coordinately regulates genes involved in their detoxification. Interestingly, both the antibiotic rifampicin and the herbal antidepressant St. John's wort activate PXR and have anticholestatic properties, which suggests that more potent, selective PXR agonists may be useful in the treatment of biliary cholestasis or other diseases characterized by the accumulation of bile acids or other toxins in the liver."
- Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor - PubMed

- Pregnane X receptor - Wikipedia

- Activation of pregnane X receptor by pregnenolone 16 α-carbonitrile prevents high-fat diet-induced obesity in AKR/J mice - PubMed

Thanks!!

 

[Hidden49]

Try Progest-e I started it a few days ago and it helps me massively and no bile impairments.

I also tried out Cypro for the first time yesterday though and that did seem to make me constipated and impair my bile. Also gave me a white tounge (Candida) but is that just a detox from my liver or did it lower my immune system in some way, I’m not sure but not gonna try it again I don’t think.

 

[mgrabs]

Interesting. I do not have this at all. I take 50mg every morning