a lot of people try to lower cortisol this way.
But these studies with a 11b-hsd1 inhibitor given to humans shows plasma cortisol levels stay the same regardless and ACTH levels rise. (ACTH rises in response to the lower conversion of cortisone -> cortisol from the enzyme inhibition, so with functional adrenals they restore the balance of cortisol levels by producing more in response). at least with up to 31% inhibition shown.
https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.12635 Wonder if their testing method is good enough? showed no changes after inhibition
The HPA axis was mildly activated with slightly increased, but still normal adrenocorticotropic hormone levels, increased total urinary corticoid excretion but unchanged plasma cortisol levels. The urinary THF/THE ratio decreased, indicating liver 11β-HSD1 inhibition. Median 11β-HSD1 enzyme inhibition in the AT reached 90% after a single dose of BI 135585, but was low (31% or lower) after 14 days of continuous treatment.
another one
https://pubmed.ncbi.nlm.nih.gov/24828020/
As reported for other 11β-HSD1-inhibitors increased concentrations of ACTH and adrenal androgen precursors were found
So if trying to lower cortisol if it's typically high, things that work like this don't look like an effective way as ACTH rises to counter it, unless on the higher end of inhibition this changes?
But these studies with a 11b-hsd1 inhibitor given to humans shows plasma cortisol levels stay the same regardless and ACTH levels rise. (ACTH rises in response to the lower conversion of cortisone -> cortisol from the enzyme inhibition, so with functional adrenals they restore the balance of cortisol levels by producing more in response). at least with up to 31% inhibition shown.
https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.12635 Wonder if their testing method is good enough? showed no changes after inhibition
The HPA axis was mildly activated with slightly increased, but still normal adrenocorticotropic hormone levels, increased total urinary corticoid excretion but unchanged plasma cortisol levels. The urinary THF/THE ratio decreased, indicating liver 11β-HSD1 inhibition. Median 11β-HSD1 enzyme inhibition in the AT reached 90% after a single dose of BI 135585, but was low (31% or lower) after 14 days of continuous treatment.
another one
https://pubmed.ncbi.nlm.nih.gov/24828020/
As reported for other 11β-HSD1-inhibitors increased concentrations of ACTH and adrenal androgen precursors were found
So if trying to lower cortisol if it's typically high, things that work like this don't look like an effective way as ACTH rises to counter it, unless on the higher end of inhibition this changes?
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