Resveratrol Stimulates Cortisol Synthesis

[haidut]

Yet another reason to avoid resveratrol. The mechanism of action is suppression of cytochrome P450, which is known as the "master detox" enzyme. I wonder if other estrogenic substances, including estrogen itself stimulate cortisol synthesis through the same mechanism. If yes, substances that boost cytochrome P450 activity should be able to inhibit cortisol synthesis. One such substance is pregnenolone and to a lesser degree DHEA. It is well known that DHEA lowers cortisol levels, and Ray has written that pregnenolone "restrains the stress reaction" which probably involves cortisol as well.


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380297/
http://www.ncbi.nlm.nih.gov/pubmed/10448061

 

[M Scott]

"The mechanism of action is suppression of cytochrome P450, which is known as the "master detox" enzyme"

Cytochrome p450's are actually a large number of enzymes. Some of them play a role in detoxification, some even do the opposite (like cyp2e1), and some are involved in hormone production.

The first paper you linked suggests is that resvertrol might cortisol by increasing the activity of two cytochrome p450's: p450scc (which makes pregnenolone from cholesterol) and cyp11b (which forms cortisol from a precursor molecule).

So it's not as simple as boosting cyp450 activity. Excessive activation of cyp11b, by resvertrol for example, might lead to high cortisol levels. But modulating p450's unrelated to cortisol may have essentially no effect.

 

[Mauritio]

Soo does P450 help the get rid of excess estrogen that is mobilizied but not excreted ?
St johns wort also stimulates P450 btw

 

[SOMO]

Soo does P450 help the get rid of excess estrogen that is mobilizied but not excreted ?
St johns wort also stimulates P450 btw

St. John's Wort is contraindicated with HIV medication because supposedly it makes the patient excrete the HIV meds too quick.

 

[cs3000]

"The mechanism of action is suppression of cytochrome P450, which is known as the "master detox" enzyme"

Cytochrome p450's are actually a large number of enzymes. Some of them play a role in detoxification, some even do the opposite (like cyp2e1), and some are involved in hormone production.

The first paper you linked suggests is that resvertrol might cortisol by increasing the activity of two cytochrome p450's: p450scc (which makes pregnenolone from cholesterol) and cyp11b (which forms cortisol from a precursor molecule).

So it's not as simple as boosting cyp450 activity. Excessive activation of cyp11b, by resvertrol for example, might lead to high cortisol levels. But modulating p450's unrelated to cortisol may have essentially no effect.

so the increased stimulation of p450scc from resveratrol should increase pregnenolone synthesis from cholesterol if it works the same way in the body - which works to counter some of the estrogenic effects of resveratrol, thats wild how it all connects like that

but this in-vivo rat study showed the opposite for cortisol

https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1002/biof.1477

The aim of this study was to clarify if resveratrol also induces such a redox shift or causes any direct enzyme inhibition that influences local cortisol production. Cortisone–cortisol conversions and changes in NADPH levels were monitored in rat liver microsomal vesicles. Cortisol production was inhibited by resveratrol in a concentration dependent manner while the intrinsic reducing and oxidizing capacity as well as the NADPH level inside the ER-derived vesicles remained unaffected. Activity measurements performed in permeabilized microsomes confirmed that resveratrol, unlike EGCG, inhibits 11β-hydroxysteroid dehydrogenase type 1 directly.

By that resveratrol actually lowers cortisol production


anyway I read inhibiting or increasing cortisol through enzymes can just cause feedback mechanism to kick in with HPA axis / adrenals production shifting in response

 

[ddjd]

so the increased stimulation of p450scc from resveratrol should increase pregnenolone synthesis from cholesterol if it works the same way in the body - which works to counter some of the estrogenic effects of resveratrol, thats wild how it all connects like that

but this in-vivo rat study showed the opposite for cortisol

https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1002/biof.1477

The aim of this study was to clarify if resveratrol also induces such a redox shift or causes any direct enzyme inhibition that influences local cortisol production. Cortisone–cortisol conversions and changes in NADPH levels were monitored in rat liver microsomal vesicles. Cortisol production was inhibited by resveratrol in a concentration dependent manner while the intrinsic reducing and oxidizing capacity as well as the NADPH level inside the ER-derived vesicles remained unaffected. Activity measurements performed in permeabilized microsomes confirmed that resveratrol, unlike EGCG, inhibits 11β-hydroxysteroid dehydrogenase type 1 directly.

By that resveratrol actually lowers cortisol production


anyway I read inhibiting or increasing cortisol through enzymes can just cause feedback mechanism to kick in with HPA axis / adrenals production shifting in response

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