1 hour ago, tryingtohelp2014 said:

 

 

Maybe an A-Ha moment....kinda never been more excited.

 

What if i showed a chart that increased the ability of St. Johns Wort to induce the CYP34A retinoic acid destoying enzyme 30x?!! Not only that, but that it upregulated all of the CYP26s and UGTs detoxifying enzymes as well?  What if we have to take a cocktail?   One part of the cocktail would be  the PXR inducing ligand, and the other to conjugate whatever the PXR mobilizes?

 

A very  very cool paper.  PXR is the master detoxification regulator.   Even when you eat foods in the safe beta carotene , it upregulates this enzyme.  Guess what doesnt upregulate it?  9-cis retinoic acid. very close to 13-cis...and im betting thats why our body doesnt kick it out.

http://www.sciencedirect.com/science/article/pii/S0925443911000275   

3.7. PXR in retinoic acid metabolism

Retinoic acid (RA) is the metabolite of vitamin A that binds to and activates the retinoic acid receptor (RAR). RAR forms a heterodimer with RXR and activates the transcription of genes associated with cell differentiation [143] and apoptosis [144], leading to inhibition of cell growth. Therefore, RAs have been used or tested as anti-cancer agents in several human cancer types [145]. However, RA resistance represents a major limit to its clinical use, which might be explained at least in part by the co-administration of a PXR agonist. Ligand activated PXR can induce expression of CYP3A and transporters such as MDR1A, MRP3 and OATP2, which accelerate RA metabolism [146]. It has been suggested that PXR antagonists might be useful in preventing RA resistance.

 

 

RFP is another PXR inducer, just like St Johns wort.  Now replace RFP on this chart with St Johns Wort.

https://www.researchgate.net/publication/11035195_Taurine_modulates_induction_of_cytochrome_P450_3A4_mRNA_by_rifampicin_in_the_HepG2_cell_line

 

A Paper showing St Johns Wort is a potent PXR inducer on the same level as RFP

https://books.google.com/books?id=uhvS9dH7nkoC&pg=PA168&lpg=PA168&dq=PXR+and+taurine&source=bl&ots=1QgilfgGNa&sig=JqDO1ZY4bpTB3OMDRjd877q-4S0&hl=en&sa=X&ved=0ahUKEwiV9JXk9P3JAhVFWSYKHT2VAYcQ6AEIVjAJ#v=onepage&q=PXR%20and%20taurine&f=false

 

 

So what these charts show is.... taking Taurine by itself doesnt induce the PXR induced CYP34A enzyme very much.  but when you take it together with a PXR inducing ligand (St Johns Wort), its like a super stacking effect increasing it exponentially! 

 

That's potentially a very good find! I'm still trying to get my head around those studies, but if STW is as an effective PXR activator as the study suggests then that along with taurine really could be really promising stuff! Dosages would be a bit of a guess, but I'm having no issues with 3g of taurine per day, so I'm going to get some STW ordered and maybe work up to over 1g/day along with the taurine and see if I can get any positive results.

1 hour ago, tanedout said:

 

That's potentially a verygood find! I'm still trying to get my head around those studies, but if STW is as an effective PXR activator as the study suggests then that along with taurine really could be really promising stuff! Dosages would be a bit of a guess, but I'm having no issues with 3g of taurine per day, so I'm going to get some STWordered and maybe work up to over 1g/day along with the taurine and see if I can get any positive results.

Ive read in a few of these studies that it takes an average of 8 days on SJW to see induction of the CYP34A....but it also says that these results are achieved using the normal amount taken in a standard herbal supplement. .. but in the chart... the higher the doses of taurine pre-loading, the better.

2 hours ago, guitarman01 said:

http://suzycohen.com/articles/stressed-out-adrenal-supplements-to-the-rescue-2/

Please write about biotin deficiency, this is what killed my husband. No one detected it and I want to alert everyone. Love your work, hope to meet you one day. J.P., Ft. Lauderdale, Florida.

so theres that. would sure like to know the story of the woman who sent that in. could not find any more info or validity on this article though.

I do have most of the symptoms listed. I'm excited to try this thing too. Ordered biotin SJW and B5 from iherb. Hoping this is the cure.

2 hours ago, guitarman01 said:

yes, I plan on taking 40mgs (40,000mcgs) of biotin per day. and I would actually welcome acne and oily skin. but I will post any positive results. I have had serious issues with ear fullness,sinus and throat pain for quite a while now, also headaches and dizziness. So if biotin defeciency has any effect with increasing cytokine productionit could be increasing any allergic type reactions. which I just got allergy tested and i am allergic to every environmental allergy you can be allergic to.

Will be looking at this next. sounds promising if accutane is still in our system after all these years. been probably about 16yrs for me. I know st johns wort when it was big in the 90s lost alot of steam because it had drug interactions with just about everything.

 

I actually do already have breakouts. My skin is crazy. I have oily and dry patches here and there. My breakouts are hormonal too I think. It's like, make up your mind, oily or dry can't be both lol. I actually just went out and bought the very expensive SK ii facial treatment essence. Helping a lot with my skin. I can see improvement already in just 4 days. Dry patches more moisturised and oily patches are not as oily. Pore have shrunk a little. Breakouts dry out faster. Overall skin tone improvement

some simple diagrams explaining how this works....

We are trying to activate the PXR thru the Herbal remedy box.... and give it an extreme boost with taurine.....

Hyperforin (the active ingredient in St Johns wort compared to Rifampicin)   .....

xenobiotic  = accutane.... detoxified thru PXR by CYP34A and UGTs for elimination.  interestingly... bile acids are another PXR promoter on the secondary path to CYP34A /UGT elimination.... so increasing your bile acids also promotes detoxification... think TUDCA and taurine/glycine.  Accutane shuts down this bile flow pathway.

So going by this diagram... Ive tried fixing a possible UGT problem with the cofactor manganese (others have tried kombucha or calcium D glucarate).... and also tried fixing the bile acid problem with taurine and glycine(others are using UDCA/TUDCA.)   Which brings us to this possibility.... just supercharge the PXR.   This alone has the ability to up-regulate all of the other enzymes that are needed.

1 hour ago, tryingtohelp2014 said:

some simple diagrams explaining how this works....

 

 

We are trying to activate the PXR thru the Herbal remedy box.... and give it an extreme boost with taurine.....

 

 

 

Hyperforin (the active ingredient in St Johns wort compared to Rifampicin)   .....

 

 

xenobiotic  = accutane.... detoxified thru PXR by CYP34A and UGTs for elimination.  interestingly... bile acids are another PXR promoter on the secondary path to CYP34A /UGT elimination.... so increasing your bile acids also promotes detoxification... think TUDCA and taurine/glycine.  Accutane shuts down this bile flow pathway.

 

So going by this diagram... Ive tried fixing a possible UGT problem with the cofactor manganese (others have tried kombucha or calcium D glucarate).... and also tried fixing the bile acid problem with taurine and glycine(others are using UDCA/TUDCA.)   Which brings us to this possibility.... just supercharge the PXR.   This alone has the ability to up-regulate all of the other enzymes that are needed.

 

Science aside a combination of all those supps did improve my health/well being, so i second your opinions

And im not going to attempt to take 600mg of biotin lol

Megadosing nutrients is rather dangerous imo

6 minutes ago, Relentless1k said:

 

Science aside a combination of all those supps did improve my health/well being, so i second your opinions

And im not going to attempt to take 600mg of biotin lol

Megadosing nutrients is rather dangerous imo

biotin would just treat onesymptom...not the cause. biotin has nothing to do with the elimination pathways...well at least isnt aneeded cofactor.

32 minutes ago, tryingtohelp2014 said:

 

biotin would just treat onesymptom...not the cause. biotin has nothing to do with the elimination pathways...well at least isnt aneeded cofactor.

 

I really wish though there was just one study one shred of evidence that accutane was still in our system after all these years. Besides just the long lasting side effects that most doctors wont even attribute to accutane. maybe when technology becomes more advance and we wouldnt need say a liver biopsy or other tissue samples (to show its still there) that no doctor would approve of to look for anyways. but man if they found anything, think of the lawsuits. you seem to be in the science/maybe medical field TRYINGTOHELP, have any connections? if we were able to excrete remnants of accutane, you could find that in a stool sample I would imagine. And boy would that say alot... (except who would ever test for that)

26 minutes ago, guitarman01 said:

I really wish though there was just one study one shred of evidence that accutane was still in our system after all these years. Besides just the long lasting side effects that most doctors wont even attribute to accutane. maybe when technology becomes more advance and we wouldnt need say a liver biopsy or other tissue samples (to show its still there) that no doctor would approve of to look for anyways. but man if they found anything, think of the lawsuits. you seem to be in the science/maybe medical field TRYINGTOHELP, have any connections? if we were able to excrete remnants of accutane, you could find that in a stool sample I would imagine. And boy would that say alot... (except who would ever test for that)

Nope, just trying to help heh.

Yeah, i can only prove this anecdotally...like ive said a few times before....i know what i felt after months of extreme exercise and calorie restriction. i felt like i was taking 4x the amount of accutane as opposed towhen i was on the drug itself.... bleeding cracked lips/nose..peeling of the hands and soles of feet...extreme joint pain, hair shedding. i just felt toxic. now when i did this .... it was alreadyyears after having stoppedaccutane! As soon as i stopped exercising, and beganeating fat,putting on weight...the side effects went away by 75%.

so im kind of 100% certain theres something still there. dont care what ANYONE says. biology 101 textbooks dont apply here... a lot of this stuff like PXR(even possible individual PXR polymorphisms)wereonly just discovered in the past few years!

8 hours ago, trantran83333 said:

 

I do have most of the symptoms listed. I'm excited to try this thing too. Ordered biotin SJW and B5 from iherb. Hoping this is the cure.

 

I actually do already have breakouts. My skin is crazy. I have oily and dry patches here and there. My breakouts are hormonal too I think. It's like, make up your mind, oily or dry can't be both lol. I actually just went out and bought the very expensive SK ii facial treatment essence. Helping a lot with my skin. I can see improvement already in just 4 days. Dry patches more moisturised and oily patches are not as oily. Pore have shrunk a little. Breakouts dry out faster. Overall skin tone improvement

I wouldnt take the b5 unless necessary, or if you find your breaking out too much if you supplement biotin.b5 competes with absorption of biotin. I tried one 500 mg pillof b5 and it really dried me out and blurred my vision. We need to hydrate our sinuses not dry them out. alot of people take high dose b5 and it works similar to accutane by drying out their oil glands.

You don't even need to dig up the cutting edge research or try and find some long lasting metabolite...

Even my pet labrador could understand that the side effectscan last as long as the benefits.

You've taken a fat soluble, toxic medication for 6 months, that accumulates with the body. One of the side effects of clear skin (technically a side effect of the originally developed chemo drug), has persisted for years since stopping the drug, yet every other side effect is'in the patient's mind'? Bollocks. Any medico who wont accept this gets the boot.

Whats good guys. I've been reading this thread for the last couple of weeks and a lot of your issues really resonate with me. I thought Idshare whats going on with me after the result of taking Accutane in 2009-2010 (17 years old) for 4 months at 40mg a day. I'm 23 now and over the last 6 years I've had one issue arise after another andcompletely rob me of living a normal life. I suffer from Brain Fog (horrible concentration, memory, word recall, problem solving and fuzzy vision), fatigue, weakness,depression (caused by all my issues. depression comes and goes),digestive issues, constipation, food allergies (Gluten, dairy, soy, corn, eggsand many other foods), dust mite allergy,dry mouth , chest congestion (struggle to talk clearly) and a lack of any social desires. Theres probably more that I'm forgetting but my memory and concentration are so bad right now that I just cant think lol. I had to drop out of College my freshman year becausethe brainfog and fatigue were to much.Ive worked differentjobs here and there over the last couple years but I eventually had to quit them to focus on my health.

So basically at 22 I hit rock bottom I was waking up with extreme body aches (body felt super heavy and like I was having some sort of immune reaction), intense head pressure and brain fog, and sinus pressure/congestion (worse when weather was cloudy or rainy), dry mouth and histamine reactions. Now one morning after my cousins wedding reception which I drank ALOT I woke up feeling 100% normal. It was the most amazing feeling ever. I could think clearly, I was energetic, ambitious, confident, extroverted, strong.It was like I was able to finally be myself and enjoy the small things. I remember just being outside in the sun felt amazing and I just felt so happy and content. Thinking this is how life should be.Now this feeling only lasted a couple hours then I crashed. I ended up feeling worse than I normally did until the next day. So this woke me up as I finally realized just how messed up I was but at the same time motivated to fix myself so I could feel like that all the time. (Keep in mind this has happened to me a couple more times)

So I went to a naturopath to see if someone could help me with all theseissues (regular doctors kept saying I was depressed after all blood test game back regular). I was told thatfood allergies/intolerancescouldbe causing my issues. So I had an IGG blood test done and cut out all food that showed up on the test. It helped me a little bit in terms of fatigue, body ache, and head pressurewise Id say I went from a 1/10 to 3. Still I felt like shit. I went back to the naturopath doctor just to be prescribed some supplements. I had a feeling this doctor dint know what was up so I stopped seeing her but maintained the diet as I did feel a bit better.

So after doing my own research I started looking into gut health. I ordered the GIEffects Stool test from Genova Diagnostics andLeaky gut test . Gut test showed a parasite infection, very low friendly bacteria and 2 pathogenicbacterial infections. Leaky gut test came back normal.So for the type of parasite infection I had according to badbugs,org only antibiotics wouldwork.So I took the recommended antibiotics which also worked to getrid of the bacterial infections. After a 2 weeks of taking the antibiotics I took another test which showed all the infections were gone. Still my symptoms remained. I started taking probiotics and drinking homemade water kefir for about a month straight which also dint really help much and gave me more head pressure (histamine reaction?). I then decided to go on a bowel cleanse made by blessed herbs. it involves fasting for 5 days drinking nothing but bentonite clay and psyllium husk shakes every 3 hours 5 times a day. After the fast my sinus issues were gone (and have stayed away)but everything else remained although the brain fog and fatigue was little bit better.I did feel like I was more in touch with my body after this cleanse. So after this cleanse I ordered the full body cleanse from thesame companywhich involvesthe kidney, liver and lymph as well as a parasite cleanse. This cleanse lasted 21 days and I could eat throughout. At the end I dint really notice any difference which was a bit depressing but what can you do lol.

So after that I started researching more and came across SIBO. So many of symptoms of SIBO are exactly what I'm dealing with. So I went to a functional medicine doctor and was tested for SIBO using the lactulose breathe test, My results came back positive with high hydrogen levels. My doctoralso tested my FREE T3 AND T4 as well as different IG markers, heavy metals and my genes through 23 and me. My Free T3 came back lowat 3.4 (bottom of range is 4.0). I also had low copper levels in my bloodwhichcould indicate excess levels of copperin my liver. My IG markers all came back normal. My 23andme results showed I have a CBS977 mutation which means I have a hard time dealingwith Sulphurs. So I started a regimen of taking 30 mg of free t3, staying on a low fodmap/low sulphur diet and taking 5 mg of berberine a day to kill off the sibo, as well as B6 supplement, DT Matrix (different liver herbs to help withdetox,and Vitamin b12 sublinguals. I'm 27 days into doing this andI definitely feel an improvement in Brain fog (30% better), energy levels are better but I wouldn't say I'm close to energetic I just don't ever feel dead tired, vision is better I feel like I'm more in the moment and everything looks more 3D and less fuzzy, my dry mouth is a bit better but it still gets dry. So doing this is definitely helping but even then I don't feel close to how I did after those rare mornings waking up in mint conditions after a night of heavy drinking. My libido is still non existent, no motivation or ambition,and I still feel emotionally flat. I just won 2 fantasy football leagues which resulted in some big payouts and Icould honestly careless. I cant remember the last time Iwas excited for anything.

Now I also had a liver ultrasound done on the 24th and I'm waiting to hear back from my doc on the results. I have a follow up to see my functional medicine doctor on the 4th. I also forgot to mention that when eating somethingI'm intolerant too like garlicI would instantly get head pressure it would feel like my head was swelling. Well I tried a bit of garlic the other day and I had no reaction. So maybe this SIBO treatment is working. Ill keep you guys updated with everything.

12 hours ago, Bobby.Digital said:

 

SIBO could explain why our body has a hard time absorbing B vitamins, esp B12

i always suspected I either had IBS or celiac desease, and went through a stage where I had leaky gut. Not to mention the gas and bloating, so very painful!

Cant wait to see a professional, the guy I'm going to seeis a doctor and a naturalpath. So hoping I'm getting the best of both worlds.

I will definitely mention SIBO to him. Thanks very much

44 minutes ago, trantran83333 said:

 

SIBO could explain why our body has a hard time absorbing B vitamins, esp B12

i always suspected I either had IBS or celiac desease, and went through a stage where I had leaky gut. Not to mention the gas and bloating, so very painful!

Cant wait to see a professional, the guy I'm going to seeis a doctor and a naturalpath. So hoping I'm getting the best of both worlds.

I will definitely mention SIBO to him. Thanks very much

Yeah I would definitely recommend the Comprehensive gut test and SIBO test. The comprehensive gut test gives you a really good insight as to what is going on with your gut.

1 hour ago, Bobby.Digital said:

 

Thanks for sharing your story. Very awesome read. Scroll back a few pages and you'll see we discussed how alcohol affects retinoid metabolism in the liver. I recommend reading Tryingtohelp2014's posts about PXR activation. " So.. St john's wort is a PXR/CYP34A inducer(just like ethanol) ---->increases isotretinoin catabolism "

It's great to have another story of someone who had a temporary cure due to alcohol ingestion. That makes me think accutane is stored in the liver. 90% of vitamin A is stored there after all..

I wouldn't assume SIBO is the root cause. You need to find WHY you have SIBO and WHY you had a parasite & bacterial infections.

I would point at accutane lowering your immunity leading to these problems. Also, accutane ruins bile flow and bile keeps SIBO at bay.

Restoring liver & gallbladder function can possibly be the cure of SIBO for some. If that doesn't solve it, herbs & elemental diet will.

15 hours ago, Bobby.Digital said:

Now one morning after my cousins wedding reception which I drank ALOT I woke up feeling 100% normal. It was the most amazing feeling ever. I could think clearly, I was energetic, ambitious, confident, extroverted, strong, and my libido was sky high.It was like I was able to finally be myself and enjoy the small things. I remember just being outside in the sun felt amazing and I just felt so happy and content. Thinking this is how life should be.

 

right....obviously this is what i take away from your story..... the feeling 100% after massive doses of ethanol so many people report the same thing.

This is where it gets confusing... treating SIBO, or biotinidase deficiency for example. getting 50 different blood tests, that say 50 different things are wrong.

Accutane up-regulates or down-regulates 200+ gene expressions.... any one of these can cause problems from hair shedding to GNMT over expression....all the way toIBS.

Its impossible to go around and treat each one of these problems individually. I think we need to try and fix the rootproblem that is altering all of these expressions. Something inside is constantly having an effect on us. This same thing is temporarily shut off when we drink. The mere fact that we can turn it off, even just for a few hours, means we arent broken..... we just have something passively altering our expressions.

The interaction of ethanol and vitamin A as a potential mechanism for the pathogenesis of Fetal Alcohol syndrome.

I also feel amazing after a lot of alcohol but not after a couple beers.

I feel like it could just also be an afterglow effect like with other drugs?

There should be some kind of blood test in existense that tests for the "remaining" accutane in the body as its retinol after all. Or a test will come, i hope.

At the moment we should focus on these two things:
1.Optimally eating, living and supplementing to support a body and all its symptoms (you would want to do this if you were healthy as well. Optimized human biology through science)

2. Getting rid of accutane from our bodies by all means wether its supplements, fasting, flushes, enemas, drugs, chelating foods etc. Doesnt really matter if its actually still in us because we cant prove it, as long as the methods we use are not harmful to health. We might even get rid of some other toxic stuff that we didnt know we had. Just really supporting all the detox pathways but really focusing on getting rid of accutane metabolites. Even if they are not really there its our best bet atm.

@tryingtohelp2014Since you are the biggest science guy in here beside me (not trying to offend anyone else), we should probably collab on making a regimen for both the reasons i mentioned above. Im very close on step 1 but have not yet begun on step 2. You able to chat on skype or something? Make a fake id user if you want to stay anonymous. I could also give you more advice on how to stay anonymous in general if you are the paranoid kind, or just dont wanna mix your real life with accutane stuff. Which i dont either at the moment. If i ever find a cure and ever become a doctor i will involve myself into this and really work on helping people as a professional. Currently im just some sick guy on the internet who has a lot of knowledge and goes through much science..

Also the feeling normal thing from alcohol could be some GABA/dopamine thing as when im on phenibut i feel like what i used to pre accutane. And thats a gabaergic that also boosts dopamine. Its wonderful to feel normal once in a while. But you can max take it 1x a week

This is unreal. I can't tell you how much i resonate with that after alcohol effect the day after and have beengetting by the past 5 years (i'm 8 years post tane) doing just this solely for that brief 6 hourperiod where libido goes back to 100%, anxiety is nonexistent, head clears, feel the trees and sunlight once again. There's something inherently wrongand I feel like we are on the cusp of finding out. Our symptoms are too coincidental and there is a pattern. I really think if we team up and put the work in this will start to gain momentum. Idon't think it's a question of if, but when,we prove that isotretinoin has the capability for direct effects on the body and brain. Roche really should be concerned, because unlike all those british and american kids that took their lives, we are living breathing revenants, and walking talking keys to the puzzle.

(I usually don't mention my libido issues but I am around85% post tane, but then again I also only took tane for only 1 month so it kind of fits the bill)

I'm all for the diet changes and the cleanses, but I am a proponent of a neurological issue, and also of genetic transcription. I have a fairly strong feeling about this. I literally run 5 kilometers every other day and yet a single cup of coffee sends my heart rate to above 150 resting for several hours. This is not normal, and it's not physical, it manifests as physical, but originates as neurological. Again, completely different from when I used to drink coffee before accutane.

Yes, the physical effects are there, the tendonitis and arthritis, the lack of cellular repair on lacerations, a completely different Delayed onset muscle soreness after exercise, and a more strange NO feeling of lactic acid buildup when I run or exercise. But, again, I can deal with the physical so this is at the back of my mind.

Anyways, my point is ethanol is not a long term solutionand tbh I've kind of met my limit on that. Relentless,I sympathize with you, I have that last move of an ssri treatment looming in my back pocket, butdon't want to go that route, as it is not my character, or who i was prior, and shouldn't be. I really think we should focus our time to find out which light switch was shut off upstairs, and if we can switch it back on.

I remember a while back, forum user"timatron" got a liver function test done and results are as follows:

"Phase 1

Caffeine Clearance 1.2 (0..5 - 1.6)

Phase 2

Glutathionation 3.1 (5.6 - 11.4)

Sulphation 26 (16 - 36)

Glucuronidation 8 (27 - 56)

Glycination 29 (30 - 53)"

One of the major detoxification pathways of accutane, glucuronidation, was very, very low. It's as if the capacity of those enzymes to work got used up due to being overburdened by retinoic acid.

He mentioned to me in a PM that he started taking calcium-d-glucarate to correct the issue but he felt worse. I think it's due to some of the accutane being carried out from the liver into the intestines for reabsorption and therefore symptoms.

"I've tried a few supps to do with glutathionation and glucuronidation earlier this year, but none did much good and in fact probably made me feel worse in particular a pill called Calcium D Glucurate, which should have helped massively."

He is now 12+ years post-accutane.

I think having the lifestyle & nutrition piece down along with various cleanses & detoxes while also including targeted nutrients specifically for getting rid of accutane is our best bet. Taurine, Glycine, calcium-d-glucarate or kombucha, St. John's Wort, etc..

I know that the herb Chelidonium majus is excellent for stimulating bile flow. Could someone with the necessary funds experiment with that? I think it could prove to be fruitful.

Also, I wonder if there are other PXR activators besides ethanol and SJW.

--

EDIT: has anyone heard of this protocol? I may check out the book

EDIT2: Check out Sauna Biohack #3: http://www.bengreenfieldfitness.com/2015/08/how-to-make-a-sauna-hotter/

I've personally used this and can confirm that it is very very effective for detoxifying the body. I'm still damaged from accutane but it definitely gets rid of LOADS of toxins & toxicants. There's ongoing research on the protocol but the research that's been done has shown MASSIVE reduction in chemical burden.

Again, I'm going to mention the name, Dietrich Klinghardt. If you guys have not looked into his work yet, you are missing out. Google his name, now. Visit his academy website and learn. Promise you it won't disappoint.

1 hour ago, yetanotheraccutanevictim said:

I remember a while back, forum user "timatron" got a liver function test done and results are as follows:

"Phase 1

Caffeine Clearance 1.2 (0..5 - 1.6)

 

Phase 2

Glutathionation 3.1 (5.6 - 11.4)

Sulphation         26 (16 - 36)

Glucuronidation 8  (27 - 56)

Glycination         29 (30 - 53)"

 

One of the major detoxification pathways of accutane, glucuronidation, was very, very low. It's as if the capacity of those enzymes to work got used up due to being overburdened by retinoic acid.

He mentioned to me in a PM that he started taking calcium-d-glucarate to correct the issue but he felt worse. I think it's due to some of the accutane being carried out from the liver into the intestines for reabsorption and therefore symptoms.

 

"I've tried a few supps to do with glutathionation and glucuronidation earlier this year, but none did much good and in fact probably made me feel worse in particular a pill called Calcium D Glucurate, which should have helped massively."

He is now 12+ years post-accutane.

 

I swear i was just reading about this again.... this is the possible negative feedback loop we could be stuck in.  Accutane suppresses UDP-glucuronosyltransferase 2B7 isoform (UGT2B7)   This is the only known enzyme known to glucurondinate 4-oxo (the main accutane metabolite)

So Accutane basically shuts off the only known way to get rid of itself.

As for phase II detoxification enzymes, retinoids, including ATRA, 9CRA, as well as the RAR panagonist 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (TTNPB, arotinoid acid) have been shown to suppress, in a concentration-dependent manner, UDP-glucuronosyltransferase 2B7 isoform (UGT2B7) mRNA expression in Caco-2 cells (64). This regulation may represent an example of a negative feedback relationship between retinoids and xenobiotics, taking into consideration that UGT2B7 was shown to be the only UGT isoform capable of catalyzing glucuronidation of ATRA and its oxidized metabolites, including 4-OH-ATRA, 4-oxo-ATRA and 5,6-epoxy-ATRA (65). The formation of these glucuronides renders the retinoids water soluble and results in their elimination in the urine. Surprisingly, this effect was not observed either in HepG2 cells or for other UGT isoforms, specifically UGT2B15 and UGT1A6, demonstrating the specificity of the inhibitory effect (64). The authors of this study however were unable to verify that UGT2B7 mRNA expression is regulated through canonical RAREs; however the observation that the RAR agonist TTNPB showed the highest potency for suppressing UGT2B7 gene expression suggests that this regulation probably occurs at the transcriptional level.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526766/

other UGT2B7 inducers.... resveratrol, rifampin,valproic acid 

This is the paper that explains everything

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129696/

It is recognized that, in addition to a large number of beneficial processes initiated by retinoids, this class of compounds can also be responsible for many deleterious effects on the body, when they either exceed physiological levels or are present in inadequate amounts.²²⁾Because of this, one can easily speculate on the consequences of the dramatic decrease of UGT2B7 expression seen in Caco-2 cells in response to retinoids. Most obviously, since UGT2B7 is involved in the elimination of excess retinoids and/or the termination of their biologicall activity, the suppression of this enzyme could result in the accumulation of excess retinoids, leading to toxicity in the cell and organism and an increase in teratogenesis and hypervitaminosis A syndrome.^23,24)UGT2B7 is also an indispensable component of the overall detoxification network. In addition to its function in modulating the activity of biologically active compounds, it also plays an essential role in controlling steady-state concentrations of compounds such as fatty acids, bile acids, prostaglandins, steroid hormones, and retinoids,²⁵⁾which are ligands for nuclear receptors, such as RXR and RAR, and other signaling pathways. A lack of UGT2B7 would allow for prolonged interactions of active retinoids with nuclear receptors and signaling pathways, potentially resulting in non-specific activation of a variety of genes. Therefore, impairment of this isoforms activity could have far reaching effects on the homeostasis of many nuclear receptor-dependant systems throughout the organism.

so yes to st. johns wart or no? any really bad sides that can come from it? I would need it for my depression more so than it helping with physical accutane sides. Just don't want to take it if it will fuck me up more.

1 hour ago, tryingtohelp2014 said:

the suppression of this enzyme could result in the accumulation of excess retinoids, leading to toxicity in the cell and organism and an increase in teratogenesis and hypervitaminosis A syndrome.^23,24)

i.e. my intracranial pressure and night blindness for the past 8 years.

Oh, andguess what treatment comes up forhypervitaminosis Ain animals and in vitro...yep, u guessed it. Taurine.

http://www.sciencedirect.com/science/article/pii/S0308814607005420

http://jn.nutrition.org/content/114/12/2256.long

This is awesome. Can't even make this stuff up. Well, we are now unofficially scientists. Not a bad way to ring in the new year!

Holy Shit.... look what else happens in your liver when you get a massive dose of Ethanol.....

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Of particular interest is the remarkable elevation of hypotaurine/taurine syntheses. Ethanol was cleared from blood linearly at 0.50 mg 0.02 mg/ml/hr, and consequently, disappeared completely in 8 hr (Fig. 1). Therefore, the increase in hypotaurine/taurine concentrations was significant while ethanol was being actively metabolized. Serum taurine levels were also elevated indicating that the increase in hepatic taurine could not be explained by impediment of the transport of this substance across the membranes. Considering the well-known role of GSH in the detoxification of reactive oxygen species and reactive metabolites, the ethanol-induced increase in the hypotaurine/taurine syntheses at the expense of the reduced generation of this tripeptide is paradoxical. It has been known that taurine exhibits considerable c~toprotective effects, which are often attributed to its antioxidant potential 2 However, taurine has minimal direct scavenging activities against oxygen-derived radicals23 Instead, hypotaurine at a concentration of several hundred J.1M has been shown to be an excellent scavenger of reactive oxygen species includi~ hydroxyl radical, hypochlorous acid, peroxynitrite and singlet oxygen . Ethanol is first biotransformed to acetaldehyde by several enzyme systems. Acetaldehyde itself or oxygen radicals generated during breakdown of ethanol have been suggested to be responsible for the initiation of lipid peroxidation25 Accordingly the ethanol-induced lipid peroxidative damage would increase the demand for antioxidant potential, which has been proposed as the mechanism of GSH depletion by some authors1' 2 However, the results in this study show that cysteine, the essential substrate for GSH synthesis, is preferentially utilized for synthesis of taurine rather than GSH in liver challenged with ethanol.

Hmmm and it wears off the next day. It also mentions the lowering of SAM/SAH ... just like Accutane does. Accutane also super elevates Taurine levels in the liver!

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Is there someone who has access to DHEA Creme? (Would be best if the person is from Europe)

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Just get DHEA pills from ur doc/endo if u cant buy them over the counter@manalesenicola

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I'll be doing testing in 2016 to see if i have some sort of infection/virus etc, SIBO +++ ill test everything including genetics to rule out any non accutane cause for the problems.If i dont find any other issues and i stick to a perfect diet and supplement regimen then the brain fog/other symptoms must be accutane's fault.

Basically im working on ruling out every single cause of my issues that could lie elsewhere, and when everything is perfect and they are still there then i know accutane is the single factor that remains to cause my issues. Either it did some permanent damage or it just takes a lot of time to reverse. And theres the theory that its still stuck in the body doing damage which i also then need to find some solution for..

I also struggle severely with learning complex math now, where as i was a grade A student in math. I still do well with stuff like biology and chemistry, cuz thats just remembering facts

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inb4 alcohol becomes a part of our recovery regimens, not many people can justify that lol

On 12/30/2015 at 6:41 AM, macleod said:

 

 

I'm all for the diet changes and the cleanses, but I am a proponent of a neurological issue, and also of genetic transcription. I have a fairly strong feeling about this. I literally run 5 kilometers every other day and yet a single cup of coffee sends my heart rate to above 150 resting for several hours. This is not normal, and it's not physical, it manifests as physical, but originates as neurological. Again, completely different from when I used to drink coffee before accutane.

Diet will have a bigger impact on the neurological issue than you think. Avoiding bad stuff is more important than some super complex diet with lots of real food. Elemental diet clears my brain fog in the same way fasting does, so accutane obviously made me/us hypersensitive to most foods.

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I cant handle coffee anymore either, or chocolate. I dont get extreme elevations but i get a really weird hard beat that skips or beats irregularly. And i can feel it all over my body and it just feels like the pump is rusty, as some door who doesnt open and close smoothly. Its like when my heart beats i can feel it sort of "lagging" like its super dry and rusty.. Only when caffeinated or so though. Not in general

Diet is still one of the only things we really can do for neurological issues. At least before we go the pharma route.

More sensitive to theobromine and theophylline than i am to caffeine in the heart ways. But caffeine affects me more mentally

Caffeine paradoxically makes me more brain fogged now where as it enhanced me prior to accutane

On 12/30/2015 at 2:23 PM, tryingtohelp2014 said:

Holy Shit.... look what else happens in your liver when you get a massive dose of Ethanol.....

 

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What we need to work on is to make sense of what to do with this though. I feel like we just clutter the thread with all these snippets of research. I filled up page after page when i went on my study binge.

Its better if the people who do research actually either have our own thread in some more science related forum or we have some "work chat" to share findings and discuss solutions.

Then just sumarize it and post the simple "Heres what it did and what to do about it" in this thread.

Remember that most the people in here are not really looking to read through the studies, they just want to ask questions and get answers.

Theres only a select few of us who really dig deep and we dont need to make it harder for other people to follow.

If you prefer to work solo thats fine but its still wise to just do research for a few days and compile your findings into a reader friendly post and then share it weekly or 2x a week or more, or less..

At least im not going to keep posting long research texts in here, ill just share my findings and what i theorize will help it..