Just read the Melcangi methylation study

Apparently 5ar1 promoter cannot be methylated.

5ar2 promoter is shown to be methylated mostly in PFS people in the spinal fluid. Methylation of this gene doesn’t happen anywhere else.

He brought up that methylation of 5ar2 could be something we are born with and that when we are exposed to a 5ar2 inhibitor, it can bind to 5ar1 instead. Methylaton of 5ar2 promoter causes 5ar2 enzymes to not be produced, so the only enzyme finasteride can bind to is 5ar1 (this can possibly explain why fin doesn’t work in reducing prostate size of people with methylated 5ar2 promoters).

5ar1 is what makes allopregnelonone via the conversion of progesterone into DHP. DHP becomes allopregnelonone from 3 hydroxysteroid dehydrogenase. This explains why PFS people have lower allopregnelonone.

This could also explain why we are sensitive to anti-androgens, because we only have 5ar1 instead of both 5ar1 and 5ar2.

How do we know if we have methylated 5ar2? No way to tell, but I would assume a lot of us do. Were we born like this or was it caused by other factors? No idea. Why does the symptoms persist?
Maybe finasteride doesn’t leave the spinal fluid?

I think the take away is we probably only have 5ar1 active and we need to be weary of anti androgens.

Also interesting study I saw, the DNMT1 inhibited mice (less methylation) exhibited less anxiety and depression. Maybe a solution would be to reduce methylation and 5ARI’s simultaneously.

Interesting study I read as well, ketones and calorie restriction inhibit Histone deacetylases (increase acetylation), which causes global demethylation. This could explain some water fasting and ketosis recoveries.

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This study blew my mind.