liver enzym CYP2C19*17 frustrates Progesteron, adrenals and MAO A

WoolPippi

Senior Member
Messages
556
Likes
1,560
Location
Netherlands
CYP2C19*17 is a liver enzym that busies itself with things like blood thinners and hormones. I'm homozygous for it which makes me an ultrafast metabolizer. Here's SNPedia about how that's classified

Ultrafast means my enzym metabolizes all its substrates superfast. Progesteron is such a substrate and CYP2C19*17 grabs it all from the blood and destroys it. I need to take MUCH MORE from this medicine than normal metabolizers. For example I'm taking 400 mg Progesteron orally every day and still get my period and PMS symptoms. It's ridiculous. 400 mg is what's prescribed to pregnant people, it's what gave the hormone its name.

Another substrate is a blood thinner like Warfarin. CYP grabs it and converts it into the effective drug. I need to get WAY LESS prescribed than a normal person otherwise I'll bleed out. Normal metabolizers only convert about 10% of Warfarin into its effective state. I do 60%. This needs to be on my medical record .

Here's a table with the known CYPs and on which substrates they work. Inhibitors and inducers are mentioned too: http://medicine.iupui.edu/clinpharm/ddis/main-table/

It's good to know how your CYPs are. It's especially important to know whether your homozygous for CYP2C19*17 because Progesteron plays such an important role in ME:
  1. it's the building block from which all cortisol is made in the adrenals.
  2. it's the one thing that helps when your MAO A gene is bust and you're running on high dopamine and noradrenaline (=norepinephrine). The catecholamines.
  3. it's needed to counter oestrogen in females. I've had oestrogen dominance all my life. PMS from hell.
I'm also using a progesteron cream (npc) so some progesteron gets to travel through my veins and do its thing before it gets to the liver and gets metabolized by that overenthusiastic CYP2C19*17 enzym.

And I make sure to stay away from its inducers such as St. Johns worth and Prednison.
Somehow one of its inhibitors, hormonal contraceptives, made me truly mad so I stay away from those too. I guess my hormones are a sensitive balance and anything can throw it off.
Xeno-oestrogen such as soya; tofu; plastics and pesticides give me oestrogen symptoms right away too.

The combination of this enzym with a homozygous MAO A gene is precarious. MAO A destroys excitatory neurotransmitters (the catecholamines) which keep a person in Fight or Flight. Another enzym that destroys dopamine is COMT. With either of these enzymes not doing their work well you get a high strung, alert person. Who's permanently taxing his body, especially the adrenals.
Progesteron gives you just the opposite: a relaxed, mellow person.
Stupid CYP.
 

Paralee

Senior Member
Messages
554
Likes
575
Location
USA
Hi, Woolpippi, I'm homozygous for it too but which is the variant. I have the hardest time figuring that out. Thanks. Oh, I see where the variant is T? I'm cc
(Man, I have a LOT of those boogers).

Funny, though, I always feel so many meds before I'm supposed to. Tamoxifen turned me into a witch (to put it nicely), couldn't take it.
 
Last edited:

WoolPippi

Senior Member
Messages
556
Likes
1,560
Location
Netherlands
could you please tell me what your estrogen symptoms are? I think a friend has these same genes
thx
PMS symptoms and big boobs on a small frame.

Pms symptoms were severe when I did not balance with progesteron cream. Mad severe. Literally. It's called PMDD then. It lasted 25 days out of a 28 day cycle.
This was when I was Zinc defficient (ate too much oat bran) and 30-35 years old (glands are dwindling down after 25).

Beware when supplementing Zinc while defficient: it may cause Copper dump. Causing madness and super wiredness for a few weeks. Worth it. But very hard. Search my posts for when I went through it. I had to put a suicide watch in place.
 

jjxx

Senior Member
Messages
121
Likes
63
PMS symptoms and big boobs on a small frame.

Pms symptoms were severe when I did not balance with progesteron cream. Mad severe. Literally. It's called PMDD then. It lasted 25 days out of a 28 day cycle.
This was when I was Zinc defficient (ate too much oat bran) and 30-35 years old (glands are dwindling down after 25).

Beware when supplementing Zinc while defficient: it may cause Copper dump. Causing madness and super wiredness for a few weeks. Worth it. But very hard. Search my posts for when I went through it. I had to put a suicide watch in place.
Hormones are such a individual fair. I have been battling them since puberty. But my case is quite the opposite, to be more precise, similar symptoms but opposite culprits.
In my case, I am progesterone intolerant. A tiny progesterone or any herb promoting it makes me extremely ill. I would also get enlarged and tender breasts approaching my period, but relieved by ESTROGEN cream!
 

Paralee

Senior Member
Messages
554
Likes
575
Location
USA
@jjxx ,I decided last week to try some soy milk for just a little estrogenic effect and felt good........until I realized I couldn't handle the oxylates, but I think I might be like you.
 

Gondwanaland

Senior Member
Messages
4,993
Likes
4,122
until I realized I couldn't handle the oxylates, but I think I might be like you.
I tried tofu for the estrogenic effect as well and it would cause me leaky gut. I thought it was oxalates, but now I think it was due to poor protein breakdown, just like with gluten (at proline bonds).
 

Paralee

Senior Member
Messages
554
Likes
575
Location
USA
sorry, I put it in a conversation (?) and it looked like it was just sitting out there for anyone to read and I couldn't delete it so I made it a bunch of gibberish. (red smiley face)

Edit, just tried again.
 

Gondwanaland

Senior Member
Messages
4,993
Likes
4,122
sorry, I put it in a conversation (?) and it looked like it was just sitting out there for anyone to read and I couldn't delete it so I made it a bunch of gibberish. (red smiley face)
Don't worry, it is a private conversation that only you and me can read.
 

jjxx

Senior Member
Messages
121
Likes
63
I tried tofu for the estrogenic effect as well and it would cause me leaky gut. I thought it was oxalates, but now I think it was due to poor protein breakdown, just like with gluten (at proline bonds).
Then soy milk would be a better option in this case?
 

jjxx

Senior Member
Messages
121
Likes
63
I suppose soy milk should have a similar protein/oxalate profile to tofu. I don't know if it is possible to react to one and not react to the other.
True. Another way to look at them is that one is solid and the other is liquid. In order for the body to digest and assimilate, solids must be broken down to small pieces then to liquid, which demands a lot of more precious physiological effort to me. I know some people have "blockage" to this simple straightforward physical process.
 

jjxx

Senior Member
Messages
121
Likes
63
@jjxx ,I decided last week to try some soy milk for just a little estrogenic effect and felt good........until I realized I couldn't handle the oxylates, but I think I might be like you.
Then have you find some relief over the years?
 

jjxx

Senior Member
Messages
121
Likes
63
@Gondwanaland Your comment regarding progesterone intolerance being B3 deficiency has been on my mind. Instead of doing research and reading, I worked it up in my head this time that it makes a certain logic sense:
Progesterone diverges tryptophan pathway from making serotonin to make B3. I am on my second day of experimenting 5mg NADH from Source Naturals. So far I have not felt any effect and am thinking double the dose tomorrow.
 

Paralee

Senior Member
Messages
554
Likes
575
Location
USA
Then have you find some relief over the years?
@jjxx , no, this was just an experiment with something I had. I might look up Black Cohosh and see what all it has in it, it's supposed to be estrogenic and help women with menopause symptoms. The soy milk was fine until the next morning.
 

Gondwanaland

Senior Member
Messages
4,993
Likes
4,122
Black Cohosh and see what all it has in it, it's supposed to be estrogenic and help women with menopause symptoms.
I tried it and it just made me hypothyroid. If you don't have thyroid problems it might work for you.
I remember reading it stimulates FSH (not sure if this is true), and my FSH is already skyhigh, so no wonder I didn't get any help from it.