Ray Peat article on progesterone for seizures - thoughts on using for medication tapering, brain healing

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I've been researching ways to heal my brain as I've gone as far as I can with diet, thyroid and stress reduction (background below if interested). I came across this article: Epilepsy and Progesterone.

This was fascinating for a few reasons. First, this person was incapacitated for years and appeared to recover quickly with progesterone. Second, this person appeared to be able to discontinue what were presumably anti-seizure medications, which are notoriously difficult to discontinue.

I am curious if anyone has thoughts on using this in real life. I was severely injured by short term use of a prescribed benzodiazepine and then cold turkeyed. I believe the original problem was low progesterone (based on symptoms and labs), but didn't see it at the time. I also believe the extent of the injury at the time was due to low neurosteroids, leaving me unprotected. My symptoms were those of severe glutamate receptor sensitivity (unable to function, tolerate sound, light, interaction, reading, TV - anything - bed bound and nonfunction until started pregabalin, an anti-seizure medication that slowed everything down).

I am now stuck functioning at 75% (much better than the previous 10% but not ideal) and tapering off this medication that is notoriously difficult to come off of. Symptoms include heart pounding, anxiety, just feeling off, and episodes of anger and depression. I never had any of this before (just insomnia). This article and others have inspired me to start on my journey. Also, since this occurred, I've only ever felt well during the peak of my luteal phase (I use an Oura ring and felt best when progesterone peaked and body temps measured +0.7 or more and 99.5 on an oral thermometer).

I am having trouble getting my temperatures to that luteal phase +0.7 even with thyroid replacement, progesterone replacement, and a Peaty diet. I plan to continue progesterone (Health Natura taken orally) until I get there and then see if I can taper off my medication and heal my brain. Pregnenolone and DHEA seem to give me agitation even in low doses, so those are out for now.

Ideas and feedback are greatly appreciated.
 

PeskyPeater

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You have indicated using Benzo, that can alter GABA-A complex. Also you feel oke in luteal phase when ALLO is high, but it's half life is short.
GABA-A agonism reduces the neurosteroid ALLO. I suppose the Benzo made your GABA-A oversensitive and is inhibiting release of ALLO, except in the luteal phase.
 

PeskyPeater

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If you cannot handle PREG which is a negative allosteric moduator for GABA-A, then you could try to agonise is partially. So when there is too much gaba it helps to reduce its tone, and when there is too little gaba activity it helps to increase it.

Angelica sinensis is a partial GABA-A agonist and has been used for insomnia too.
 
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You have indicated using Benzo, that can alter GABA-A complex. Also you feel oke in luteal phase when ALLO is high, but it's half life is short.
GABA-A agonism reduces the neurosteroid ALLO. I suppose the Benzo made your GABA-A oversensitive and is inhibiting release of ALLO, except in the luteal phase.
I suspect that my brain is having difficulty making allo, so when the ovaries are making progesterone and thus there is enough substate to increase the allo, I get an improvement. I do hope that allopregnanolone gan heal the GABA system - there are several papers suggesting this is true. When I have more energy, I'll write up what. know with references and experiences. Progesterone is a calcium channel blocker, so that may help. I suspect there are problems with pushing the progesterone pedal so hard, but for now it's the best option that I've got. Funnily enough, i just came across the interview where Ray Peat talks about the alcoholic / opiate addict who cured himself with progesterone. He started the first night with a whole bottle of Progest-E and continued with 2 bottles a week for about 5 months. This is crazy high for a male and it's just a testimony. But it is intriguing and suggests that perhaps progesterone can actually result in lasting beneficial changes in the brain that has been damaged by substances. In my case, my benzo was prescribed, it was a short period of a few months, it was a low dose and it wasn't daily. But I suspect that my neurosteroids were already compromised by years of stress, and possibly micronutrients like thiamine, though who knows. It's all pretty crappy at the end of the day, and although I understand the problem to some degree, finding a solution is hard. There is the "time heals" but if you are in a level of excruciating mental pain that makes life unlivable, then you've got a pretty big problem (where I was until very recently).
 

PeskyPeater

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I dont know how you take it but, oral DHEA is converted to it's sulfate DHEAS and that is more potent to reduce GABA currents than DHEA itself.

I suspect that my brain is having difficulty making allo, so when the ovaries are making progesterone and thus there is enough substate to increase the allo, I get an improvement. I do hope that allopregnanolone gan heal the GABA system - there are several papers suggesting this is true. When I have more energy, I'll write up what. know with references and experiences. Progesterone is a calcium channel blocker, so that may help. I suspect there are problems with pushing the progesterone pedal so hard, but for now it's the best option that I've got. Funnily enough, i just came across the interview where Ray Peat talks about the alcoholic / opiate addict who cured himself with progesterone. He started the first night with a whole bottle of Progest-E and continued with 2 bottles a week for about 5 months. This is crazy high for a male and it's just a testimony. But it is intriguing and suggests that perhaps progesterone can actually result in lasting beneficial changes in the brain that has been damaged by substances. In my case, my benzo was prescribed, it was a short period of a few months, it was a low dose and it wasn't daily. But I suspect that my neurosteroids were already compromised by years of stress, and possibly micronutrients like thiamine, though who knows. It's all pretty crappy at the end of the day, and although I understand the problem to some degree, finding a solution is hard. There is the "time heals" but if you are in a level of excruciating mental pain that makes life unlivable, then you've got a pretty big problem (where I was until very recently).
I dont think allo is going to help because its half life is so short, when released it activates the GABA-A and also reducing its sensitivity. While the GABA-A in turn is going to reduce ALLO release, stuck in a vicious circle.
And when you keep adding PREG or progesterone and convert to ALLO it in turn is going to downregulate GABA-A, keeping the loop active.
You have to break it.

I think a combination of Angelica with Ziziphus jujuba seed extract and Bupleurum could help do that
...
for example:
Regulation of GABAA and 5-HT Receptors Involved in Anxiolytic Mechanisms of Jujube Seed: A System Biology Study Assisted by UPLC-Q-TOF/MS and RT-qPCR Method

Results showed that SZJ extract (250 μg/mL) significantly up-regulated the mRNA level of GABRA1 and GABRA3 as well as HTR1A, HTR2A, and HTR2B in non-H2O2 treated SH-SY5Y cells. However, it exerted an inhibitive effect on the overexpressed mRNA of GABRA1, GABRA2, HTR1A, and HTR2A in H2O2 treated SH-SY5Y cells. Taken together, our findings suggest that anxiolytic mechanisms of SZJ mostly involve the regulation of GABAergic and serotonergic synapse pathways, especially a two-way modulation of GABRA1, HTR1A, and HTR2A. Our current results provide potential direction for future investigation of SZJ as an anxiolytic agent.
 
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PeskyPeater

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There are two types of GABAARs that differ by subneuronal distribution, function, structure and pharmacology: synaptic and extrasynaptic receptors (Belelli and Lambert, 2005; Carver and Reddy, 2013). Synaptic GABAARs contain mainly α1, α2 and α3 subunits, along with β subunit variants and the γ2 subunit (Fritschy and Panzanelli, 2014), and are located at the synaptic membrane (Somogyi et al., 1996; Essrich et al., 1998), where they mediate a rapid and transitory inhibition (phasic current) following the intermittent release of high (millimolar) concentrations of GABA from the presynaptic terminals (Farrant and Nusser, 2005); importantly, these receptors are sensitive to benzodiazepines as well as Allo (Hájos et al., 2000)
https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.13843
Neurosteroid biosynthesis down-regulation and changes in GABAA receptor subunit composition: a biomarker axis in stress-induced cognitive and emotional impairment
 

mostlylurking

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I've been researching ways to heal my brain as I've gone as far as I can with diet, thyroid and stress reduction (background below if interested). I came across this article: Epilepsy and Progesterone.

This was fascinating for a few reasons. First, this person was incapacitated for years and appeared to recover quickly with progesterone. Second, this person appeared to be able to discontinue what were presumably anti-seizure medications, which are notoriously difficult to discontinue.

I am curious if anyone has thoughts on using this in real life. I was severely injured by short term use of a prescribed benzodiazepine and then cold turkeyed. I believe the original problem was low progesterone (based on symptoms and labs), but didn't see it at the time. I also believe the extent of the injury at the time was due to low neurosteroids, leaving me unprotected. My symptoms were those of severe glutamate receptor sensitivity (unable to function, tolerate sound, light, interaction, reading, TV - anything - bed bound and nonfunction until started pregabalin, an anti-seizure medication that slowed everything down).

I am now stuck functioning at 75% (much better than the previous 10% but not ideal) and tapering off this medication that is notoriously difficult to come off of. Symptoms include heart pounding, anxiety, just feeling off, and episodes of anger and depression. I never had any of this before (just insomnia). This article and others have inspired me to start on my journey. Also, since this occurred, I've only ever felt well during the peak of my luteal phase (I use an Oura ring and felt best when progesterone peaked and body temps measured +0.7 or more and 99.5 on an oral thermometer).

I am having trouble getting my temperatures to that luteal phase +0.7 even with thyroid replacement, progesterone replacement, and a Peaty diet. I plan to continue progesterone (Health Natura taken orally) until I get there and then see if I can taper off my medication and heal my brain. Pregnenolone and DHEA seem to give me agitation even in low doses, so those are out for now.

Ideas and feedback are greatly appreciated.
Have you considered the role of thiamine? It might play a part and might be helpful. I have found high dose thiamine to be very helpful.

For your consideration:

Deficencies Created When Taking Medication "Lyrica (pregabalin) is an anti-epileptic drug, also called an anticonvulsant –boosts potassium levels, depletes the body of thiamine(B1) & vitamin D"
But I suspect that my neurosteroids were already compromised by years of stress, and possibly micronutrients like thiamine, though who knows.
You just posted again and included this about thiamine so I see that you are aware of this issue.

"The absence of any increase in glutamate levels in the nonvulnerable FPC suggests that a glutamate-mediated excitotoxic mechanism may be responsible for the selective cerebral vulnerability in thiamine deficiency."

I'm more familiar with the use of thiamine to resolve the issues of Parkinson's Disease; I thought there might be some overlap.
 
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I dont know how you take it but, oral DHEA is converted to it's sulfate DHEAS and that is more potent to reduce GABA currents than DHEA itself.


I dont think allo is going to help because its half life is so short, when released it activates the GABA-A and also reducing its sensitivity. While the GABA-A in turn is going to reduce ALLO release, stuck in a vicious circle.
And when you keep adding PREG or progesterone and convert to ALLO it in turn is going to downregulate GABA-A, keeping the loop active.
You have to break it.

I think a combination of Angelica with Ziziphus jujuba seed extract and Bupleurum could help do that
...
for example:
Regulation of GABAA and 5-HT Receptors Involved in Anxiolytic Mechanisms of Jujube Seed: A System Biology Study Assisted by UPLC-Q-TOF/MS and RT-qPCR Method

Results showed that SZJ extract (250 μg/mL) significantly up-regulated the mRNA level of GABRA1 and GABRA3 as well as HTR1A, HTR2A, and HTR2B in non-H2O2 treated SH-SY5Y cells. However, it exerted an inhibitive effect on the overexpressed mRNA of GABRA1, GABRA2, HTR1A, and HTR2A in H2O2 treated SH-SY5Y cells. Taken together, our findings suggest that anxiolytic mechanisms of SZJ mostly involve the regulation of GABAergic and serotonergic synapse pathways, especially a two-way modulation of GABRA1, HTR1A, and HTR2A. Our current results provide potential direction for future investigation of SZJ as an anxiolytic agent.
Great thought. I did try it, but it didn't seem to do much. Honestly, I've read all the studies on allo and progesterone and that still seems to be my best hope. Allo appears to actually correct the GABA system, helping it to work better. Progesterone is a calcium channel blocker. High dose progesterone is the only thing that has come close to giving me any hope of relief. Pretty much every other supplement has done almost nothing sadly.
 

Izzybelle

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I've been researching ways to heal my brain as I've gone as far as I can with diet, thyroid and stress reduction (background below if interested). I came across this article: Epilepsy and Progesterone.

This was fascinating for a few reasons. First, this person was incapacitated for years and appeared to recover quickly with progesterone. Second, this person appeared to be able to discontinue what were presumably anti-seizure medications, which are notoriously difficult to discontinue.

I am curious if anyone has thoughts on using this in real life. I was severely injured by short term use of a prescribed benzodiazepine and then cold turkeyed. I believe the original problem was low progesterone (based on symptoms and labs), but didn't see it at the time. I also believe the extent of the injury at the time was due to low neurosteroids, leaving me unprotected. My symptoms were those of severe glutamate receptor sensitivity (unable to function, tolerate sound, light, interaction, reading, TV - anything - bed bound and nonfunction until started pregabalin, an anti-seizure medication that slowed everything down).

I am now stuck functioning at 75% (much better than the previous 10% but not ideal) and tapering off this medication that is notoriously difficult to come off of. Symptoms include heart pounding, anxiety, just feeling off, and episodes of anger and depression. I never had any of this before (just insomnia). This article and others have inspired me to start on my journey. Also, since this occurred, I've only ever felt well during the peak of my luteal phase (I use an Oura ring and felt best when progesterone peaked and body temps measured +0.7 or more and 99.5 on an oral thermometer).

I am having trouble getting my temperatures to that luteal phase +0.7 even with thyroid replacement, progesterone replacement, and a Peaty diet. I plan to continue progesterone (Health Natura taken orally) until I get there and then see if I can taper off my medication and heal my brain. Pregnenolone and DHEA seem to give me agitation even in low doses, so those are out for now.

Ideas and feedback are greatly appreciated.

I can relate my own experience with benzodiazapines and maybe this will help. I cold-turkeyed off benzos and every muscle in my body went into spasm and stayed that way -- muscle knots in every single part of my body, including my face.

So I tried a muscle relaxant called Flexeril which helped a little. Other Peaty things that helped (but didn't solve the problem) were high dose niacinamide, high dose glycine, and progesterone. It's been years now that I've had this problem and I found out that I had some underlying infections that may have contributed. I'm also recently undergoing a great deal of stress again so I tried a little Xanax and it did seem to loosen the muscles somewhat. Then I read that Valium has more muscle relaxing properties so I got a doctor to switch me to that and now I take it regularly, starting with a higher dose and tapering down slowly and it is helping, perhaps healing the problem but it will take some time. I plan to taper down to the lowest dose where I still feel results and then taper off completely when I feel healed enough. I know that your situation is a bit different, but I would say that progesterone is definitely helpful. I've recently started some B1 (but it is too soon to say if it is helping), restarted the niacinamide and glycine but at lower doses. Something to try in small doses and occasionally for heart pounding and anxiety would be propanolol. it blocks adrenaline (which could be causing some of your symptoms) and is typically used for high blood pressure but off-label use is for anxiety or panic attacks and it is not addictive. Perhaps research it and decide for yourself. It has been around a long time and I believe is safe for short term use. Peat has mentioned it somewhere, just can't remember where. Some people with high blood pressue stay on it for years at high doses. Hope this helps.
 

PeskyPeater

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Great thought. I did try it, but it didn't seem to do much. Honestly, I've read all the studies on allo and progesterone and that still seems to be my best hope. Allo appears to actually correct the GABA system, helping it to work better. Progesterone is a calcium channel blocker. High dose progesterone is the only thing that has come close to giving me any hope of relief. Pretty much every other supplement has done almost nothing sadly.
sorry what did you try exactly?
 
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sorry what did you try exactly?
Jujube seed (I responded to it above with the full quote included). Almost all plant supplements are incredibly disappointing despite much promising data. I usually start low and slow and increase to high doses then taper down. I have not found benefit from any of them and I've tried many, always in isolation to try to see the effects. I do feel words better than a year ago, but no where near the vitality that I once had. It has been an event of mass destruction, like a hurricane. I know that a city destroyed can be rebuilt with the right materials, workers and tools, I am just trying to make sure I have all of that. A tough road to be sure. My focus now is N acetyl carnitine, N acetylcysteine (not Peaty but has some potential to reset the glutamate system and I do take thyroid) and agmatine (poorly studied abut appears to be an NMDA antagonist so seems beneficial for my situation temporarily.) Otherwise, Peaty eating, low stress, and spending my life savings on progesterone (being dramatic but it's expensive to take the amount that I take - it does help immensely at the right, very high, dose). I also take T3 (can't take T4, never could, so there's a problem there the pre-dates this).
 
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I can relate my own experience with benzodiazapines and maybe this will help. I cold-turkeyed off benzos and every muscle in my body went into spasm and stayed that way -- muscle knots in every single part of my body, including my face.

So I tried a muscle relaxant called Flexeril which helped a little. Other Peaty things that helped (but didn't solve the problem) were high dose niacinamide, high dose glycine, and progesterone. It's been years now that I've had this problem and I found out that I had some underlying infections that may have contributed. I'm also recently undergoing a great deal of stress again so I tried a little Xanax and it did seem to loosen the muscles somewhat. Then I read that Valium has more muscle relaxing properties so I got a doctor to switch me to that and now I take it regularly, starting with a higher dose and tapering down slowly and it is helping, perhaps healing the problem but it will take some time. I plan to taper down to the lowest dose where I still feel results and then taper off completely when I feel healed enough. I know that your situation is a bit different, but I would say that progesterone is definitely helpful. I've recently started some B1 (but it is too soon to say if it is helping), restarted the niacinamide and glycine but at lower doses. Something to try in small doses and occasionally for heart pounding and anxiety would be propanolol. it blocks adrenaline (which could be causing some of your symptoms) and is typically used for high blood pressure but off-label use is for anxiety or panic attacks and it is not addictive. Perhaps research it and decide for yourself. It has been around a long time and I believe is safe for short term use. Peat has mentioned it somewhere, just can't remember where. Some people with high blood pressue stay on it for years at high doses. Hope this helps.
Thank you so much for sharing your story. It makes me feel less alone. My problems have been primarily all mental with some physical (mostly nerve issues in my legs with electric sensations). I did try all of those Peaty things and have considered finding someone to put me on Valium for a slow taper. I went the pregabalin route instead - not sure if that was a good move or not but it's done. The adrenaline is gone with a ton of progesterone interestingly - it took a few months. I also reduced my T3 by half (was on 37mcg now), but want to titrate up. But you've give me some things to consider, and I appreciate it. Hoping that you find much healing yourself.
 

Izzybelle

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Thank you so much for sharing your story. It makes me feel less alone. My problems have been primarily all mental with some physical (mostly nerve issues in my legs with electric sensations). I did try all of those Peaty things and have considered finding someone to put me on Valium for a slow taper. I went the pregabalin route instead - not sure if that was a good move or not but it's done. The adrenaline is gone with a ton of progesterone interestingly - it took a few months. I also reduced my T3 by half (was on 37mcg now), but want to titrate up. But you've give me some things to consider, and I appreciate it. Hoping that you find much healing Dyourself.
Do you mind if I ask which benzodiazapine you were taking? Was is Klonopin? Because I had been taking Xanax for some time sporadically and was down to about .5 to 1.0 mg at night -- with occasional higher doses if I felt really stressed -- and was having muscle issues that I never connected to the Xanax use. I was concerned though that I was addicted because I couldn't sleep without the nightly dose, so my doctor switched me to Klonopin where I was supposed to taper down and that was when all hell broke loose. My muscles started to knot up all over within a month and that was when I cold-turkeyed. Scared the hell out of me. Apparently Stevie Nicks (of the band Fleetwood Mac) has some nightmare stories online about Klonopin use and how it ruined her life.

I'm glad to know that you are making progress with progesterone. I'd be interested in knowing how high a dose of progesterone you are taking which has helped your anxiety. I was taking a fairly high dose for a while and it made me feel calmer, but it wasn't healing my muscles all that much. It took a lot of consideration to go back on some kind of benzo again, but it looked to me like Valium was my best option as other muscle relaxants were only having minimal effect. I'm thinking of upping the progesterone as I taper off, just still considering how high of a dose of progesterone I should use.

postcript: Another member also mentioned Vitamin D, which I think has also helped me. Red light, sunshine and Vitamin D seems to cure a lot of things:) Also, I was having trouble getting my temps up for years. T3 and T3/T4 combo didn't do anything. Then I had some retinyl palmitate in my freezer that I bought a while ago and didn't know if I needed t ior not, so last summer I tried some very high doses and my temps shot up to 98.9 or 99 degrees every day. Since it is winter now and I get less sun I only take a smaller dose now and then and eat a little liver and my temps aren't quite as high but more normal 98.6 or 98.7 during the day. Magnesium may also be playing role as I take that when I feel that I haven't gotten enough in my diet. Not advocating this or anything because I just don't know enough about the mechanism behind it, just know that vitamin A and magnesium are necessary for proper thyroid function, hence progesterone as well. Just some food for thought.
 
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PeskyPeater

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Jujube seed (I responded to it above with the full quote included). Almost all plant supplements are incredibly disappointing despite much promising data. I usually start low and slow and increase to high doses then taper down. I have not found benefit from any of them and I've tried many, always in isolation to try to see the effects. I do feel words better than a year ago, but no where near the vitality that I once had. It has been an event of mass destruction, like a hurricane. I know that a city destroyed can be rebuilt with the right materials, workers and tools, I am just trying to make sure I have all of that. A tough road to be sure. My focus now is N acetyl carnitine, N acetylcysteine (not Peaty but has some potential to reset the glutamate system and I do take thyroid) and agmatine (poorly studied abut appears to be an NMDA antagonist so seems beneficial for my situation temporarily.) Otherwise, Peaty eating, low stress, and spending my life savings on progesterone (being dramatic but it's expensive to take the amount that I take - it does help immensely at the right, very high, dose). I also take T3 (can't take T4, never could, so there's a problem there the pre-dates this).
But wait a minute, were you trying these herbals while also using that synthetic modified GABA pregabalin ?
 

PeskyPeater

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I understand you have been reading up on neurosteroids and how they modulate GABA complex. But they are not going to help you fix this.
AS I understand it, the GABA complex has negative feedback systems in place that keep tight control over its downstream effects . Meaning that when positive allosteric modulaters or negative modulators act upon the GABA cells, the net effect is always to desensitize accordingly. So assuming you have been using pregabalin, of which it's function is not understood by the creators, there is a fat chance it's use is counterproductive by preventing returning to homeostasis.
Then you have to take a step back and look at it from a higher perspective, meaning its imperative to eliminate that factor of uncertainty, the use of pregabalin
 
K

Kaur Singh

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I am curious if anyone has thoughts on using this in real life. I was severely injured by short term use of a prescribed benzodiazepine and then cold turkeyed. I believe the original problem was low progesterone (based on symptoms and labs), but didn't see it at the time. I also believe the extent of the injury at the time was due to low neurosteroids, leaving me unprotected. My symptoms were those of severe glutamate receptor sensitivity (unable to function, tolerate sound, light, interaction, reading, TV - anything - bed bound and nonfunction until started pregabalin, an anti-seizure medication that slowed everything down).
Symptoms include heart pounding, anxiety, just feeling off, and episodes of anger and depression. I never had any of this before (just insomnia).

I find it useful when you describe your symptoms.

I had all of the above - and I have not touched any meds.


Have you tried anti-serotonin substances? Cypro etc
you may have mentioned it elsewhere.
the anger the depression the insomnia

because what estrogen in excess does to tryptophan metabolism
favoring the formation of neurotoxic substances
niacinamide
is worth exploring

Bs? (careful with B6)
You can do the supp route
or you can do the liver/ and other organs route.

have you noticed the effect muscle meats have on you?
as in aggravating more of the anger depression insomnia

if so,
You can back of for a bit and when things get better,
you can try them again.

also, there may be something useful here:

how's your Ca consumption?
saturated fats? protein? carbs? calories?
you D levels?
your cholesterol?
have you tried E?
aspirin?
etc

No need to answer me
just that there is a lot to play with here
The article you mention,
Peat has suggestions and ideas there as well.

the latest podcast with Kate Deering
might be of interest to you
as the topic is progesterone
 
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OP
T
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Messages
96
I find it useful when you describe your symptoms.

I had all of the above - and I have not touched any meds.


Have you tried anti-serotonin substances? Cypro etc
you may have mentioned it elsewhere.
the anger the depression the insomnia

because what estrogen in excess does to tryptophan metabolism
favoring the formation of neurotoxic substances
niacinamide
is worth exploring

Bs? (careful with B6)
You can do the supp route
or you can do the liver/ and other organs route.

have you noticed the effect muscle meats have on you?
as in aggravating more of the anger depression insomnia

if so,
You can back of for a bit and when things get better,
you can try them again.

also, there may be something useful here:

how's your Ca consumption?
saturated fats? protein? carbs? calories?
you D levels?
your cholesterol?
have you tried E?
aspirin?
etc

No need to answer me
just that there is a lot to play with here
The article you mention,
Peat has suggestions and ideas there as well.

the latest podcast with Kate Deering
might be of interest to you
as the topic is progesterone
I really appreciate your thoughtful reply. I have found it astonishing the number of symptoms that others have had related to hormone imbalance. I also find it fascinating that some women seem to do fine after menopause (or do they?) I am not in menopause yet, but perimenopause. Of course, women (and men) have trouble throughout life for various reasons with accompanying hormonal issues.

I have tried cypro, but perhaps should give it another try. Antihistamines tend to make me feel kind of foggy, and this fog often lasts most of the day, so I don't do well with them. I have also tried aspirin, including with baking soda, and after a few days by stomach just gets angry. I even tried enteric coated. So I just can't seem to crack that one, though I do keep trying.

I have tried varying doses of niacinamide from 500mg to 2000mg without noticing much. I am always paranoid about the whole methylation thing with it, but maybe that's silly.

I am now trying a month of Thorne multivitamin elite, which seems to have all the right forms of various vitamins. I'd rather do it with food, but it gets hard. I do have liver that I try to eat a few times a week. It's from a local farm.

D levels are pretty good at around 60 the last time I checked.

I haven't noticed a problem with muscle meats but should probably add in some collagen for balance. Calcium consumption is quite a lot, I supplement E. I've always had low T3 and high cholesterol. T3 I've taken for a long time with levels now in the middle of the range. They seem to stay there even if I double the T3, so I guess my liver chews up any extra. I take 4mcg four times a day. It keep me from feeling desperately depressed.

I try to limit PUFA, eat a fair bit of carbs as OJ and milk, and fats are mostly butter and coconut oil with some olive oil.

The only things that seems to have a noticeable and often huge impact is progesterone. But sometimes I have to take a lot. I did listen to the podcast where Ray Peat mentioned a friend who was an alcoholic and opiate addict. He just kept taking Progest-E until he felt better. I think it was the whole bottle (3000+mg) the first night, and two bottles a week thereafter for about 5 months. He apparently stopped drinking and doing drugs and got a job. I guess what I got from the story is that you need what you need and you should take it until you feel better. So I am going to try that. I've never gotten to a whole bottle before. I had wondered about vitamin E toxicity with that much progest-e but Ray Peat never mentioned it.
 

PeskyPeater

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I 've done more research about this GABA complex and neurosteroids etc. not just for the fun of it, but it interest me to figure out, because of similar GABA issues with a hypothyroid friend that I am assisting.

How do benzo's alter the GABA sensitivity ? read this
Diazepam-induced loss of inhibitory synapses mediated by PLCδ/ Ca2+/calcineurin signalling downstream of GABAA receptors

How do neurosteroids affect the GABA sensitivity? read this
Physiological role for GABAA receptor desensitization in the induction of long-term potentiation at inhibitory synapses
GABAA receptors (GABAARs) are pentameric ligand-gated ion channels distributed throughout the brain where they mediate synaptic and tonic inhibition. Following activation, these receptors undergo desensitization which involves entry into long-lived agonist-bound closed states. Although the kinetic effects of this state are recognised and its structural basis has been uncovered, the physiological impact of desensitization on inhibitory neurotransmission remains unknown. Here we describe an enduring form of long-term potentiation at inhibitory synapses that elevates synaptic current amplitude for 24 h following desensitization of GABAARs in response to agonist exposure or allosteric modulation. Using receptor mutants and allosteric modulators we demonstrate that desensitization of GABAARs facilitates their phosphorylation by PKC, which increases the number of receptors at inhibitory synapses. These observations provide a physiological relevance to the desensitized state of GABAARs, acting as a signal to regulate the efficacy of inhibitory synapses during prolonged periods of inhibitory neurotransmission.

What else influences the GABA complex signaling possible implication for alternative treatment? read these
Co-regulation of GABAA receptors by neurosteroids and protein kinases
GABAA Receptor Phosphorylation and Functional Modulation in Cortical Neurons by a Protein Kinase C-dependent Pathway*

Looks like PKC is an alternative mechanism to gaba regulation with possibility of restorative treatment

Stumbled upon this about licorice root and it reducing glutamate via GABA-B and it's effect on PKC.
Natural Product Isoliquiritigenin Activates GABAB Receptors to Decrease Voltage-Gate Ca2+ Channels and Glutamate Release in Rat Cerebrocortical Nerve Terminals.
Reduction in glutamate release is a key mechanism for neuroprotection and we investigated the effect of isoliquiritigenin (ISL), an active ingredient of Glycyrrhiza with neuroprotective activities, on glutamate release in rat cerebrocortical nerve terminals (synaptosomes). ISL produced a concentration-dependent inhibition of glutamate release and reduced the intraterminal [Ca2+] increase. The inhibition of glutamate release by ISL was prevented after removing extracellular Ca2+ or blocking P/Q-type Ca2+ channels. This inhibition was mediated through the γ-aminobutyric acid type B (GABAB) receptors because ISL was unable to inhibit glutamate release in the presence of baclofen (an GABAB agonist) or CGP3548 (an GABAB antagonist) and docking data revealed that ISL interacted with GABAB receptors. Furthermore, the ISL inhibition of glutamate release was abolished through the inhibition of Gi/o-mediated responses or Gβγ subunits, but not by 8-bromoadenosine 3',5'-cyclic monophosphate or adenylate cyclase inhibition. The ISL inhibition of glutamate release was also abolished through the inhibition of protein kinase C (PKC), and ISL decreased the phosphorylation of PKC. Thus, we inferred that ISL, through GABAB receptor activation and Gβγ-coupled inhibition of P/Q-type Ca2+ channels, suppressed the PKC phosphorylation to cause a decrease in evoked glutamate release at rat cerebrocortical nerve terminals.
 

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