I was doing some questions with Bing chat and discovered a new possible avenue for treatment. Bing chat was reluctant as per usual but I finagled the information I needed eventually.
Anyways, this will focus on eliminating epigenetic changes that may be caused by SSRIs, and Post Isotretinoin syndrome, PFS.
It told me on RxISK.org there was a possible treatment report using a drug that blocks the enzyme Aldehyde dehydrogenase 24.
That specific enzyme could be involved in the pathogenisis of PSSD. It can modulate the activity of neurosteroids in the brain and also serotonin receptors.
A drug that blocks ALDH24 could reduce the accumulation of retinoic acid and reverse epigenetic changes that cause PSSD.
I asked the chat why we as PSSD suffers would have accumulation of retinoic acid in the first place, With people who are taking isotretinion its more straight forward they are taking a vitamin A derivative and it accumulates in them so why does it accumulate in us?
SSRIs interfere with the metabolism of RA by inhibiting the enzyme Cyp26A1.
Therefore RA builds up in the body and effects the steroid and serotonin receptors.
I then asked is the inhibition of that enzyme permanent it said it is not permanent but it may take a long time to recover after stopping use of SSRIs
I opened a separate chat afterward looking for compounds that exist today that could block ALDH24, I found curcumin, disulfiram, butenafine, olaparib, zeaxanthin.
I then cross-referenced each of them with this forum to see if people have had experiences with those compounds. I found some accounts of curcumin and disulfiram helping but none of them mentioning this mechanism.
The other ones besides zeaxathin had no results. The zeaxathin had 1 result of a user who mentioned it in a post titled 5HT and steroidogenisis which goes in depth about some other proposed ways of helping such as SCFA's and HDACi.
In that post, it also suggests there is a block of steroid genisis in the brain.
The other 3 I could not find any accounts I think one is a cancer drug but I hope we can find some more substances that inhibit ALDH24 and test this theory.
Potential treatment ALDH24 Blocker
Re: Potential treatment ALDH24 Blocker
I don't know who has the data on the genetics of PSSD people but maybe we could do a test to see if any one has any genetic polymorphism regarding Cyp26A1 enzyme maybe people that develop PSSD don't have the ability to stop inhibition through that enzyme while people who don't get it have that enzyme functioning in a hyper state.
I asked bing chat for some potential polymorphisms that may contribute to or reduce risk of PSSD
here are the results
"According to the web search results, one of the mutations that increases the enzyme activity of Cyp26A1 is rs138478634, which causes a missense mutation that reduces the enzymatic activity of Cyp26A1 and increases the retinoic acid levels1. This mutation may make Cyp26A1 less likely to be inhibited by substances that normally bind to its active site, such as retinoic acid or its derivatives. However, this mutation is very rare and has only been reported in a few cases of microtia1.
Another possible mutation that could increase the enzyme activity of Cyp26A1 is a deletion or a loss-of-function mutation in the promoter region of Cyp26A1, which could reduce the negative regulation of its transcription by retinoic acid or other factors. This could result in higher expression and activity of Cyp26A1, and lower levels of retinoic acid. However, I could not find any evidence of such a mutation in the web search results."
I speculate people who have the first polymorphism have severe PSSD and people with the second may have no chance of getting it at all.
I asked bing chat for some potential polymorphisms that may contribute to or reduce risk of PSSD
here are the results
"According to the web search results, one of the mutations that increases the enzyme activity of Cyp26A1 is rs138478634, which causes a missense mutation that reduces the enzymatic activity of Cyp26A1 and increases the retinoic acid levels1. This mutation may make Cyp26A1 less likely to be inhibited by substances that normally bind to its active site, such as retinoic acid or its derivatives. However, this mutation is very rare and has only been reported in a few cases of microtia1.
Another possible mutation that could increase the enzyme activity of Cyp26A1 is a deletion or a loss-of-function mutation in the promoter region of Cyp26A1, which could reduce the negative regulation of its transcription by retinoic acid or other factors. This could result in higher expression and activity of Cyp26A1, and lower levels of retinoic acid. However, I could not find any evidence of such a mutation in the web search results."
I speculate people who have the first polymorphism have severe PSSD and people with the second may have no chance of getting it at all.
Re: Potential treatment ALDH24 Blocker
Check out Grant Genereux's books here. All free. And all about vitamin A being an actual poison, not a nutrient.
https://ggenereux.blog/my-ebooks/
Garrett Smith has been making a lot of headway, took Grant's work and ran with it. Nutrition Detective on YouTube:
Love Your Liver Livestream #127: INFERTILITY & “vit” A, Copper, & Mercury! #toxicbiletheory
https://www.youtube.com/live/oi27Wj8jP3 ... jdswpQmn-q
----------
Not sure about blocking an ALDH pathway. My understanding is that "vitamin" (poison) A is detoxed through those pathways in the form of retinaledhyde. Most of Garrett's work revolves around naturally improving the ADH and ALDH pathways, and avoiding things that slow them down.
One of the theories is that retinol binding protein is meant to *detoxify* vitamin A, as it's a toxin.
Garrett's livestreams are great, and I recommend them to anyone willing to watch them.
-----------
Twitter post he made here, titled:
""vitamin" A Deficiency Doesn't Exist: What I Learned By Examining Human Studies"
https://twitter.com/NutriDetect/status/ ... 9286975489
-----------
Food for thought. I think Garrett has the best approach. And the fact that serum vitamin A often goes UP HIGHER when people stop eating/drinking vitamin A -- the liver is getting rid of it, slowly. Crashes, flare-ups....might all be related to bile dumping.
The fact that PRSD (post retinoid sexual dysfunction) exists...not a coincidence. I used to eat TONS of liver, ate tons of cheese, drank tons of kefir, drank gallons of carrot juice, ate tons of oranges, and sweet potatoes, and yes, even leafy greens, which most people think of as extremely healthy. Eggs too. I used to make omelettes almost daily with 5 eggs and a bunch of cheese. Was a big fan of liverwurst too. These are all LOADED with vitamin A, and I also took a bunch of Nutrisorb A on top of that because of some other health guy I was following.
I very well think it could all be related. Detoxing from vitamin A is an extremely slow process, with Garrett saying to buckle up for at least a few years. He's had at least one person in his LYL (Love Your Liver) network who has reversed their liver cirrhosis from stage 4 to stage 2 or lower, and continuing to improve. I've been in contact with one member there who has told me 7 years into PSSD, he's had results 10 months into the program. Enjoyed kissing his wife for the first time in that many years since PSSD. So very encouraging.
I haven't been doing the program strictly, at all. Only more recently I'm taking it to heart. The theory is also that ALL vitamin A is the same, doesn't matter if it's synthetic or food-based, it's all toxic.
So. Just a theory. But this could make a lot of sense. Not everyone is going crazy with vitamin A like I did, but between heavy metal toxicity, pollution, poor gut motility, damage from antibiotics and more -- it's very possible that smaller amounts of vitamin A have built up over a long period of time and us PSSD sufferers have gotten the short end of the stick as a result.
Hopefully someone finds this useful. This is the most cutting edge stuff I'm aware of and I think offers the most hope, though it's not particularly exciting. Long and slow. But if the theory is correct --could be huge. Grant himself has been on this low A diet for 9 years and is in excellent health, which you can see on his blog.
https://ggenereux.blog/my-ebooks/
Garrett Smith has been making a lot of headway, took Grant's work and ran with it. Nutrition Detective on YouTube:
Love Your Liver Livestream #127: INFERTILITY & “vit” A, Copper, & Mercury! #toxicbiletheory
https://www.youtube.com/live/oi27Wj8jP3 ... jdswpQmn-q
----------
Not sure about blocking an ALDH pathway. My understanding is that "vitamin" (poison) A is detoxed through those pathways in the form of retinaledhyde. Most of Garrett's work revolves around naturally improving the ADH and ALDH pathways, and avoiding things that slow them down.
One of the theories is that retinol binding protein is meant to *detoxify* vitamin A, as it's a toxin.
Garrett's livestreams are great, and I recommend them to anyone willing to watch them.
-----------
Twitter post he made here, titled:
""vitamin" A Deficiency Doesn't Exist: What I Learned By Examining Human Studies"
https://twitter.com/NutriDetect/status/ ... 9286975489
-----------
Food for thought. I think Garrett has the best approach. And the fact that serum vitamin A often goes UP HIGHER when people stop eating/drinking vitamin A -- the liver is getting rid of it, slowly. Crashes, flare-ups....might all be related to bile dumping.
The fact that PRSD (post retinoid sexual dysfunction) exists...not a coincidence. I used to eat TONS of liver, ate tons of cheese, drank tons of kefir, drank gallons of carrot juice, ate tons of oranges, and sweet potatoes, and yes, even leafy greens, which most people think of as extremely healthy. Eggs too. I used to make omelettes almost daily with 5 eggs and a bunch of cheese. Was a big fan of liverwurst too. These are all LOADED with vitamin A, and I also took a bunch of Nutrisorb A on top of that because of some other health guy I was following.
I very well think it could all be related. Detoxing from vitamin A is an extremely slow process, with Garrett saying to buckle up for at least a few years. He's had at least one person in his LYL (Love Your Liver) network who has reversed their liver cirrhosis from stage 4 to stage 2 or lower, and continuing to improve. I've been in contact with one member there who has told me 7 years into PSSD, he's had results 10 months into the program. Enjoyed kissing his wife for the first time in that many years since PSSD. So very encouraging.
I haven't been doing the program strictly, at all. Only more recently I'm taking it to heart. The theory is also that ALL vitamin A is the same, doesn't matter if it's synthetic or food-based, it's all toxic.
So. Just a theory. But this could make a lot of sense. Not everyone is going crazy with vitamin A like I did, but between heavy metal toxicity, pollution, poor gut motility, damage from antibiotics and more -- it's very possible that smaller amounts of vitamin A have built up over a long period of time and us PSSD sufferers have gotten the short end of the stick as a result.
Hopefully someone finds this useful. This is the most cutting edge stuff I'm aware of and I think offers the most hope, though it's not particularly exciting. Long and slow. But if the theory is correct --could be huge. Grant himself has been on this low A diet for 9 years and is in excellent health, which you can see on his blog.
Who is online
Users browsing this forum: No registered users and 3 guests