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On 3/13/2021 at 6:37 PM, Aaron76 said:Serotonin syndrome is when theres too much systemic serotonin and not enough systemic dopamine. I've had this for 30 years post accutane. It causes hypertension, agitation, irritation, autonomic imbalance, gut issues, joint issues, sleep and mood issues, etc. I tested very high for 5hiaa several years ago. Doctor didn't even pay attention to it, probably because she didn't know what to do about it.
I think the issue is twofold. The radioactive drug is still in us, which causes reversible brain damage, which depletes dopamine and raises serotonin. Currently doing the following: 3 now l phenylalanine, 6 seagate seaweed, 1 pure encapsulations mcha, and 1 perfect beef liver. Will keep the board posted.
Forgot to mention, brown seaweed has always been the number one food recommendation from my biofeedback machine from day one. Apricots and pumpkin usually come in after that, then bananas and black currant. Crucifers and garlic typically show up a bit farther down the list. Beef liver is all over the map. Sometimes it's in the top two foods, and sometimes it's way down the list.
I think the machine can detect the Retinoic acid, and wants to detox it with brown seaweed. And also tries to counterbalance it with carotenoid rich apricots and pumpkin. This machine is russian tech from 2012, and sweet potatoes weren't big in russia back then, or they'd probably show up high on the list also.
Tyrosine shows up in the brain supplements section from time to time, but I think phenylalanine is better than tyrosine since tyrosine is a non essential amino, unlike L Phenylalanine, which is essential. If the drug is still in the body then the brown seaweed is likely the most important thing, with beef liver next.
If I do brown seaweed by itself, it completely wipes out my brain cholesterol levels. If I take it with beef liver, this negative effect does not happen. Vitamin A is important for cholesterol biosynthesis.
I am not attempting to start an argument or a flame war here... I am not convinced by any of this. A brief search in peer reviewed literature and I cannot find anything regarding a chronic serotonin syndrome. It may be something else you have that shares similar presentation, but I doubt it is actual serotonin syndrome. I have first hand experience with patients that have presented with SS. People die from this if severe enough and not caught early. A mild presentation is possible depending on the causative agent and may be non-life threatening with self resolution. That said, it's an acute onset. It does not last 30 years. You'd be the first person in human history if so. As said, I believe it is something else. Up regulation of serotonin, upregulation of receptors, impaired metabolism, impaired negative feedback mechanisms etc. If you have lower levels of dopamine then you should be describing those symptoms as well which you have not.
Nothing exists in my readings suggests thatthis drug is radioactive only that it is teratogenic to pregnant females. Many other environmental and epigenetic factors can cause reductions in dopamine to serotonin production. You have no way to pin point with clear accuracy that this is the cause, if at all.Therefore, taking whatever you're taking in hopes it can cross the highly selective blood brain barrier in hopes to cause cellular detox and regulation of cellular function is wishful thinking, not to mention the results unmeasurable; therefore,produce a placebo like response. One could simple state that by eating: Pumpkin seeds, brown seaweed, apricots -etc. have similar effect to a person going from a sedentary lifestyle filled with McDonalds cheeseburgers to a life of exercise, and proper eating. No doubt that eating foods that support a healthy function will impact a persons overall health state and therefore mental state. You cannot come back here to state that this simple action single handedly improved dopamine/serotonin levels. You cannot extract it because the effects are systemic. You also don't have baseline data to show improvement. You also have not ruled out any other factors that could be the cause. Therefore all of this is folly.
I'm sorry, but I believe you are misinformed. You have admirable efforts however..
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637283/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445202/
21 hours ago, k3tchup said:I am not attempting to start an argument or a flame war here... I am not convinced by any of this. A brief search in peer reviewed literature and I cannot find anything regarding a chronic serotonin syndrome. It may be something else you have that shares similar presentation, but I doubt it is actual serotonin syndrome. I have first hand experience with patients that have presented with SS. People die from this if severe enough and not caught early. A mild presentation is possible depending on the causative agent and may be non-life threatening with self resolution. That said, it's an acute onset. It does not last 30 years. You'd be the first person in human history if so. As said, I believe it is something else. Up regulation of serotonin, upregulation of receptors, impaired metabolism, impaired negative feedback mechanisms etc. If you have lower levels of dopamine then you should be describing those symptoms as well which you have not.
Nothing exists in my readings suggests thatthis drug is radioactive only that it is teratogenic to pregnant females. Many other environmental and epigenetic factors can cause reductions in dopamine to serotonin production. You have no way to pin point with clear accuracy that this is the cause, if at all.Therefore, taking whatever you're taking in hopes it can cross the highly selective blood brain barrier in hopes to cause cellular detox and regulation of cellular function is wishful thinking, not to mention the results unmeasurable; therefore,produce a placebo like response. One could simple state that by eating: Pumpkin seeds, brown seaweed, apricots -etc. have similar effect to a person going from a sedentary lifestyle filled with McDonalds cheeseburgers to a life of exercise, and proper eating. No doubt that eating foods that support a healthy function will impact a persons overall health state and therefore mental state. You cannot come back here to state that this simple action single handedly improved dopamine/serotonin levels. You cannot extract it because the effects are systemic. You also don't have baseline data to show improvement. You also have not ruled out any other factors that could be the cause. Therefore all of this is folly.
I'm sorry, but I believe you are misinformed. You have admirable efforts however..
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637283/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445202/
Only teratogenic to pregnant females??? You sure?
Are youa doctor?
I took isotretinoin 2 years ago (when I was 18) and recently had a brain scan because since my treatment, I have constantly some sort ofpressure on the left side of my body, especially my head. I was afraid it would be MS. They discovered white matter lesions that can't be explained but it's not MS. Could this be related?I can't be sure it's due to isotretinoin because I was born too soon and that could also be the reason, said my neurlogist. But the thing is, I never had any problems util after treatment. I don't have any sexual sides but I experience periods of extreme anxiety and lethargy. It's like I can't handle stress anymore. The only thing that works for me is working out and running to relief anxiety.
2 hours ago, Lifesuckshard said:I took isotretinoin 2 years ago (when I was 18) and recently had a brain scan because since my treatment, I have constantly some sort ofpressure on the left side of my body, especially my head. I was afraid it would be MS. They discovered white matter lesions that can't be explained but it's not MS. Could this be related?I can't be sure it's due to isotretinoin because I was born too soon and that could also be the reason, said my neurlogist. But the thing is, I never had any problems util after treatment. I don't have any sexual sides but I experience periods of extreme anxiety and lethargy. It's like I can't handle stress anymore. The only thing that works for me is working out and running to relief anxiety.
Thanks for sharing your story
What is the follow up for treating the lesions? What can be done about them if anything?
Short back story: A year and a half ago, I foolishly took the advice of a dermatologist to take a third round of Accutane to clear up my persistent acne. I was skeptical and knew it wasn't a good idea considering how much it permanently changed my skin type by the two prior courses, (I now have uncomfortable bone dry skin) However, to cut a long story short I stupidly decided to listen to the ''expert'' and give Accutane a third shot. I have never regretted a decision more in my life.
A couple years before that I had Lasik eye surgery which cost approx. $6,000 to correct my horrible vision I've always had. The results were amazing. However, a few months into taking my third Accutane course I noticed a considerable change in my vision, especially when in indoor settings at University, shopping centers and while driving in low light and at night. I immediately stopped taking Accutane and went back to the place which conducted my Lasik eye procedure to ask what was happening. He agreed there had been a deterioration in my eye sight and agreed that Accutane was to blame as it shrinks your oil glands which can cause vision problems. When I asked if the damage was permanent he said ''Yes.''
A year later, my vision has not improved. I've had to go back to wearing glasses whenever I attend University classes or drive in low light. Years later, my skin has never returned back to its normal state. I now have to use multiple heavy moisturizers with facial oils, sometimes multiple times a day to relieve the dryness. I also have to apply Vaseline everyday inside my nostrils to stop the dryness in there. This has been absolutely devastating to me. I kick myself everyday that i did this to myself.
I want to ask is there ANY possible way to reverse any of the damage Accutane has done to my sebaceous glands? Is there any hope at all? I read another post on here by another member that going to see a endocrinologist might be an idea, but does anyone have any ideas or suggestions? I don't care if i get all my acne back, I just want my vision and my normal skin type back.
11 hours ago, TrueJustice said:Thanks for sharing your story
What is the follow up for treating the lesions? What can be done about them if anything?
From now on, I have a brain scan every six months to follow up the lesions and hopeit's not degenerative. My neurologist said these lesions are "atypical" and there isn't a clear pattern like there is with MS. It'sjust random white spots. It's too soon to tell if it's progressive or not. It's possible that these lesions are due to neuroinflammation and that could also explain my random anxiety.
On 3/18/2021 at 7:00 AM, Calcified said:Only teratogenic to pregnant females??? You sure?
Are youa doctor?
Yes, I'm sure.
Merriam-Webster dictionary describes teratogenic as "...relating to, or causing development malformations." The oxford dictionary states teratogen, "an agent or factor which causes malformation of an embryo."
An embryo pertains to females, especially pregnant females or females wanting to become pregnant. Therefore, I stand corrected when I state "teratogen/teratogenic."
I refuted the claim that it is "radioactive." Scholarly articles to not label accutane as "radioactive." Only, teratogenic. It is my belief that you misunderstand these terms and casually relate them together as one generalization of harmfulness. And I won't disagree that the side effects of accutane aren't "harmful" to some extent, butthey are not teratogenic unless a female is attempting to develop an embryo. They are not teratogenic to males because we do not develop embryos...
My credentials because you call them into question:
I have a Bachelors in Nursing which includes human anatomy, physiology, and pharmacology.I have an active practice license.I am a current graduate student that will graduate with a Doctorate in Nursing with Advanced Practice in Nurse Anesthesia. I have completed my graduate level pharmacology course, anesthesia pharmacology course, advanced human anatomy & physiology, and am starting human cadaveranatomy next week as part of my curriculum.
If you wish to correct me I would ask for your credentials to make such claims.
7 hours ago, k3tchup said:Yes, I'm sure.
Merriam-Webster dictionary describes teratogenic as "...relating to, or causing development malformations." The oxford dictionary states teratogen, "an agent or factor which causes malformation of an embryo."
An embryo pertains to females, especially pregnant females or females wanting to become pregnant. Therefore, I stand corrected when I state "teratogen/teratogenic."
I refuted the claim that it is "radioactive." Scholarly articles to not label accutane as "radioactive." Only, teratogenic. It is my belief that you misunderstand these terms and casually relate them together as one generalization of harmfulness. And I won't disagree that the side effects of accutane aren't "harmful" to some extent, butthey are not teratogenic unless a female is attempting to develop an embryo. They are not teratogenic to males because we do not develop embryos...
My credentials because you call them into question:
I have a Bachelors in Nursing which includes human anatomy, physiology, and pharmacology.I have an active practice license.I am a current graduate student that will graduate with a Doctorate in Nursing with Advanced Practice in Nurse Anesthesia. I have completed my graduate level pharmacology course, anesthesia pharmacology course, advanced human anatomy & physiology, and am starting human cadaveranatomy next week as part of my curriculum.
If you wish to correct me I would ask for your credentials to make such claims.
I havent actually claimed anything and I believe SS isn't happening, but there's a alot of info out there about isotrentoin and dopamine, not just being unsafe for pregnant females.
A lot of people report mental health issues after treatment. I watched on tv they sometimes don't give it to depressed people.
Its actually good a qualified medical person is posting, you may have info we are not aware of.
Yeah full respect for nurses and all they do - most do an incredible job and should be paid more imo!!
All I can say is were gonna need more of them in the future, nursing Accutane victims well before their time and everyone else fucked over by the medical system
Mindboggling to say the least isnt it.
On 3/17/2021 at 10:29 AM, k3tchup said:I am not attempting to start an argument or a flame war here... I am not convinced by any of this. A brief search in peer reviewed literature and I cannot find anything regarding a chronic serotonin syndrome. It may be something else you have that shares similar presentation, but I doubt it is actual serotonin syndrome. I have first hand experience with patients that have presented with SS. People die from this if severe enough and not caught early. A mild presentation is possible depending on the causative agent and may be non-life threatening with self resolution. That said, it's an acute onset. It does not last 30 years. You'd be the first person in human history if so. As said, I believe it is something else. Up regulation of serotonin, upregulation of receptors, impaired metabolism, impaired negative feedback mechanisms etc. If you have lower levels of dopamine then you should be describing those symptoms as well which you have not.
Nothing exists in my readings suggests thatthis drug is radioactive only that it is teratogenic to pregnant females. Many other environmental and epigenetic factors can cause reductions in dopamine to serotonin production. You have no way to pin point with clear accuracy that this is the cause, if at all.Therefore, taking whatever you're taking in hopes it can cross the highly selective blood brain barrier in hopes to cause cellular detox and regulation of cellular function is wishful thinking, not to mention the results unmeasurable; therefore,produce a placebo like response. One could simple state that by eating: Pumpkin seeds, brown seaweed, apricots -etc. have similar effect to a person going from a sedentary lifestyle filled with McDonalds cheeseburgers to a life of exercise, and proper eating. No doubt that eating foods that support a healthy function will impact a persons overall health state and therefore mental state. You cannot come back here to state that this simple action single handedly improved dopamine/serotonin levels. You cannot extract it because the effects are systemic. You also don't have baseline data to show improvement. You also have not ruled out any other factors that could be the cause. Therefore all of this is folly.
I'm sorry, but I believe you are misinformed. You have admirable efforts however..
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637283/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445202/
I've abandoned the quantum biofeedback based beef liver/brown seaweed regimen in favor of daily L Phenylalanine to address the 30 year issue of post accutane dopamine depletion, which causes long term serotonin syndrome. Anytime dopamine levels are chronically low, serotonin will be chronically high, which is why my 5hiaa reading was off the charts. It's not rocket science.
Accutane induced Rxr and rar modification of d1 and d2 receptors disrupts the dopaminergic system. Daily supplementation with L phenylalanine hopefully can restore normal dopaminergic activity in the brain and body. Time will tell. Already I'm experiencing a detox reaction from L Phenylalanine, with massive amounts of loose stools. I suspect this is mostly stored water and salt coming from the abdomen (ascites).
Phenylalanine/dopamine is important for the regulation of the pancreas, gallbladder, thyroid, and kidneys. Let's see what mr ignorant aka ketchup has to say about that.
20 hours ago, AnthonyAndrew said:This is my story of the damage accutane has done to my eyesight. Please any advice would be appreciated.Short back story: A year and a half ago, I foolishly took the advice of a dermatologist to take a third round of Accutane to clear up my persistent acne. I was skeptical and knew it wasn't a good idea considering how much it permanently changed my skin type by the two prior courses, (I now have uncomfortable bone dry skin) However, to cut a long story short I stupidly decided to listen to the ''expert'' and give Accutane a third shot. I have never regretted a decision more in my life.
A couple years before that I had Lasik eye surgery which cost approx. $6,000 to correct my horrible vision I've always had. The results were amazing. However, a few months into taking my third Accutane course I noticed a considerable change in my vision, especially when in indoor settings at University, shopping centers and while driving in low light and at night. I immediately stopped taking Accutane and went back to the place which conducted my Lasik eye procedure to ask what was happening. He agreed there had been a deterioration in my eye sight and agreed that Accutane was to blame as it shrinks your oil glands which can cause vision problems. When I asked if the damage was permanent he said ''Yes.''
A year later, my vision has not improved. I've had to go back to wearing glasses whenever I attend University classes or drive in low light. Years later, my skin has never returned back to its normal state. I now have to use multiple heavy moisturizers with facial oils, sometimes multiple times a day to relieve the dryness. I also have to apply Vaseline everyday inside my nostrils to stop the dryness in there. This has been absolutely devastating to me. I kick myself everyday that i did this to myself.
I want to ask is there ANY possible way to reverse any of the damage Accutane has done to my sebaceous glands? Is there any hope at all? I read another post on here by another member that going to see a endocrinologist might be an idea, but does anyone have any ideas or suggestions? I don't care if i get all my acne back, I just want my vision and my normal skin type back.
My skin after isotretinoin is dry, thin and fragile, what it was during the course, it never went back to normal even after years. I'm thinking could growth hormone help in this situtation. I would like to hear if somebody has experience with it or opinions about it.
11 hours ago, Calcified said:
I havent actually claimed anything and I believe SS isn't happening, but there's a alot of info out there about isotrentoin and dopamine, not just being unsafe for pregnant females.
A lot of people report mental health issues after treatment. I watched on tv they sometimes don't give it to depressed people.
Its actually good a qualified medical person is posting, you may have info we are not aware of.
There could be some connection.
https://www.karger.com/Article/Fulltext/355849
This systematic review on parkinson's disease speaks on the retinoic acid and retinol receptors. It states that retinoic acid influences D1 & D2 receptor expression due to a retinoic acid complex being present within the genes that control receptor sites. However, what the authors describe is different than the assumptions I made thinking that too much retinol which is what isotretinoin is would be bad causing some sort of down regulation of dopamine receptors causing the side effects we see such as depression. This is not the case as higher levels of retinoic acid encourage/promote better signal transduction (messenger action). But one could postulate that such high levels cause inverse receptor action (causes the exact opposite I just described to occur)that makes dopamine when binding to dopamine receptors in CNS less likely to produce a full response due to changes in receptor expression for excessive retinoic acid enzyme activity from excessive retinol from isotretinoin/accutane.
An interesting thing to do would be to do a prospective study-a study that goes forward in time that follows those on accutane to see if they develop CNS related disorders/diseases later in life. However, because these types of studies are not only quite lengthy they are also quite expensive; therefore, to the scientific research community where is the incentive? Most prospective studies cut off at 4-7 years whereas people can live for decades, it's just not feasible to see if we can make a connection between say Parkinson's Disease later in life and accutane use. Parkinson's disease is a disruption of dopamine production deep in the brain due to degeneration of the basal ganglia.
Another theory is because accutane causes or leads to early apoptosis, program cell death, which increase turnover maybe that has something to do with CNS cells.
7 hours ago, Aaron76 said:I've abandoned the quantum biofeedback based beef liver/brown seaweed regimen in favor of daily L Phenylalanine to address the 30 year issue of post accutane dopamine depletion, which causes long term serotonin syndrome. Anytime dopamine levels are chronically low, serotonin will be chronically high, which is why my 5hiaa reading was off the charts. It's not rocket science.
Accutane induced Rxr and rar modification of d1 and d2 receptors disrupts the dopaminergic system. Daily supplementation with L phenylalanine hopefully can restore normal dopaminergic activity in the brain and body. Time will tell. Already I'm experiencing a detox reaction from L Phenylalanine, with massive amounts of loose stools. I suspect this is mostly stored water and salt coming from the abdomen (ascites).
Phenylalanine/dopamine is important for the regulation of the pancreas, gallbladder, thyroid, and kidneys. Let's see what mr ignorant aka ketchup has to say about that.
I can see the full text article because of my school's library, but you won't so I will link to the abstract:
https://pubmed.ncbi.nlm.nih.gov/23962262/
That said, this paper in the International Journal of Dermatology proves your hypothesis of excessive, long term serotonin syndrome to be false and opposite.
Here is an exert from the paper:As a result, isotretinoin increases the expression of postsynaptic D2 dopamine receptors and simultaneously activates the transcription of tyrosine hydroxylase (TyrOHase, which plays a role in dopamine synthesis) and the transcription of monoamine oxidaseB (MAO, which deactivates dopamine after reuptake into the cell). As a consequence, a relative dopamine deficiency develops in the affected neural networks. Furthermore, ATRA stabilizes the mRNA and inhibits the degradation of the 5HT1Areceptor, thereby increasing its presynaptic concentration, enhancing serotonin reuptake and causing inhibition of serotonin secretion. In addition, isotretinoin increases the intracellular concentration of serotonin transporter (SERT) by both stabilizing its mRNA and inducing the expression of relevant genes. The SERT takes part in the reuptake of synaptic serotonin. In combination, these processes decrease serotonin signaling.
You don't have serotonin syndrome and probably have the exact opposite.
I wish you luck in your dopamine quest and that you don't cause any down regulation of your own production; however, that may not be possible anyway due to enzyme activity converting L-phenylalanine to L-tyrosine to L_DOPA as it maybe a rate limiting reaction anyway. And even if you produce more, you need receptors for them to bind to which accutane could have permanently altered making dopamine less effective.
9 hours ago, k3tchup said:There could be some connection.
https://www.karger.com/Article/Fulltext/355849
This systematic review on parkinson's disease speaks on the retinoic acid and retinol receptors. It states that retinoic acid influences D1 & D2 receptor expression due to a retinoic acid complex being present within the genes that control receptor sites. However, what the authors describe is different than the assumptions I made thinking that too much retinol which is what isotretinoin is would be bad causing some sort of down regulation of dopamine receptors causing the side effects we see such as depression. This is not the case as higher levels of retinoic acid encourage/promote better signal transduction (messenger action). But one could postulate that such high levels cause inverse receptor action (causes the exact opposite I just described to occur)that makes dopamine when binding to dopamine receptors in CNS less likely to produce a full response due to changes in receptor expression for excessive retinoic acid enzyme activity from excessive retinol from isotretinoin/accutane.
An interesting thing to do would be to do a prospective study-a study that goes forward in time that follows those on accutane to see if they develop CNS related disorders/diseases later in life. However, because these types of studies are not only quite lengthy they are also quite expensive; therefore, to the scientific research community where is the incentive? Most prospective studies cut off at 4-7 years whereas people can live for decades, it's just not feasible to see if we can make a connection between say Parkinson's Disease later in life and accutane use. Parkinson's disease is a disruption of dopamine production deep in the brain due to degeneration of the basal ganglia.
Another theory is because accutane causes or leads to early apoptosis, program cell death, which increase turnover maybe that has something to do with CNS cells.
If you take isotrentoin long enough you stop peeling, so something seems to bechanging at a receptor level, but not sure.
I can handle a very high retinol intake now, which doesn't move my serum retinol levels unless I consume 100,000iu retinyl palmitate daily, and it goes up slow, but goes down fast.
Again thanks for contributing.
Not paying any attention to other posts for now. Tried going with just Phenylalanine and thyroid pain came back. Conducted a biofeedback scan of the thyroid, and beef liver and brown seaweed were toward the top of the foods list. Took them and within 45 minutes the thyroid pain was gone.
A simple google search of accutane radioactive, or accutane radiation, reveals multiple websites that show accutane induced radioactivity in multiple parts of the body. these studies are not hard to find. A child could find them. The thyroid is likely the most sensitive organ in the body when it comes to radiation.
Serotonin syndrome is simply the presence of too much serotonin in the body. There is no time limit, and ssri intake is not the only way it can occur. The problem with american doctors is a false sense of superiority. They have a med degree so they are superior to everyone else, when in reality the exact opposite is usually the case due to their misguided, pharmaceutically based training.
Will be going with L Phenylalanine, whole beef liver, and brown seaweed daily, and report later. Take care.
Vitamin A is a key regulator of the dopaminergic system. It is also key for endogenous cholesterol biosynthesis. If fake vitamin A is still there, these systems will be impaired.
Adequate dopamine is crucial for lymphatic system pumps and flow. Inadequate dopamine means impaired lymphatic function.
I think truejustice was absolutely right about the importance of the lymphatic system with all of this. Whole beef liver and brown seaweed pills without L Phenylalanine produced no detox reaction. When I did all three, I had massive loose stools and diarrhea, indicating a detox reaction. Will continue to do all three daily and report experiences later.
12 hours ago, Quinc said:Hey all, look into PPARy and accutanes effect on it. It seems that sebaceous glands can be affected long term and PPARy agonists may help reverse this reduction in lipid production.
I also looked into this. The most potent PPARy agonists are thiazolidinediones (TZD). These are used to treat diabetes, psoriasis and ulcerative colitis. It also blocks ALDH1a3, this enzym is needed to synthezise al trans retinoic acid. It could even help against depression because it's neuroprotective.
https://pubmed.ncbi.nlm.nih.gov/16675962/
https://www.sciencedirect.com/science/article/abs/pii/S0009279718314881
Specific antagonist of retinoid toxicity in mice
A M Standeven et al. Toxicol Appl Pharmacol. 1996 May.
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Abstract
AGN 193109 was recently identified as a potent retinoic acid receptor (RAR) antagonist in vitro. The purpose of the present study was to determine if AGN 193109 functions as an RAR antagonist in vivo and thus could prevent and/or treat retinoid toxicity. Female hairless mice were treated topically for 5 consecutive days with the synthetic retinoic acid receptor agonist (E)-4-[2-(5,6,7,8- tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propen-1-yl]benzoic acid (TTNPB) alone or in the presence of a 1-, 4-, or 16-fold molar excess of AGN 193109. TTNPB caused skin flaking, skin abrasions, and splenomegaly, and these effects were blocked in a dose-dependent fashion by AGN 193109 cotreatment. In the same model, AGN 193109 also decreased topical irritation induced by the natural RAR agonist, all-trans-retinoic acid. To determine if topical AGN 193109 could block toxicity induced by an oral retinoid, mice were treated by gavage with TTNPB (0.75 mumol/kg/day) and topically with 0, 0.3, or 1.2 mumol/kg/day of AGN 193109 for 4 days. TTNPB treatment alone caused cutaneous irritation and weight loss, and these effects were inhibited by AGN 193109 cotreatment. To determine if AGN 193109 could be used to treat preexisting retinoid toxicity, mice were pretreated topically on Days 1-2 with TTNPB (0.72 mumol/kg/day) and then treated topically on Days 3-5 with 0, 1.44, 7.2, or 36.0 mumol/kg of AGN 193109. TTNPB pretreatment caused precipitous weight loss and, in the absence of AGN 193109 intervention, 60% mortality. AGN 193109 treatment at all dose levels significantly accelerated recovery of body weight and prevented death in TTNPB-intoxicated mice. These data demonstrate that AGN 193109 is a potent RAR antagonist and a potential antidote of retinoid intoxication in vivo. In addition to potential clinical applications in the prevention and treatment of retinoid toxicity, AGN 193109 should provide a powerful experimental tool for the elucidation of retinoid biology.
6 hours ago, Lifesuckshard said:I also looked into this. The most potent PPARy agonists are thiazolidinediones (TZD). These are used to treat diabetes, psoriasis and ulcerative colitis. It also blocks ALDH1a3, this enzym is needed to synthezise al trans retinoic acid. It could even help against depression because it's neuroprotective.
https://pubmed.ncbi.nlm.nih.gov/16675962/
https://www.sciencedirect.com/science/article/abs/pii/S0009279718314881
What benefits would this provide, if it's for sebaceous glands , are we talking about dry skin,lips, eye's ?.
And do you have to keep taking it to get the benefits?
8 hours ago, f*ckaccutane said:What benefits would this provide, if it's for sebaceous glands , are we talking about dry skin,lips, eye's ?.
And do you have to keep taking it to get the benefits?
It would make your skin produce more oil and improve insulin resistance. My bloodsugar is always very high since accutane and I can't gain any weight or muscles no matter how much I workout or what I eat. A side effect of this medication is general weight gainbut it reduces abdominal fat. Post-accutane, the skinbarrier can't lock water and moisture very well and TZD's should improve the skin barrier. I don't know if this would also help for dry eyes. The question would be how long you should take it.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500869/
It was used to treat frontal fibrosing alopecia and there was one patient who was treated with 15 mg pioglitazone daily and after 8 months, the disease was stabilized. There was no further hair loss or inflammation after one year post-treatment follow-up.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500869/
A patient with progressive MS was treated with 45 mg pioglitazone daily for 3 years. After these 3 years, there was clinical improvement without adverse events.
On 3/22/2021 at 5:00 AM, Lifesuckshard said:It would make your skin produce more oil and improve insulin resistance. My bloodsugar is always very high since accutane and I can't gain any weight or muscles no matter how much I workout or what I eat. A side effect of this medication is general weight gainbut it reduces abdominal fat. Post-accutane, the skinbarrier can't lock water and moisture very well and TZD's should improve the skin barrier. I don't know if this would also help for dry eyes. The question would be how long you should take it.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500869/
It was used to treat frontal fibrosing alopecia and there was one patient who was treated with 15 mg pioglitazone daily and after 8 months, the disease was stabilized. There was no further hair loss or inflammation after one year post-treatment follow-up.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500869/
A patient with progressive MS was treated with 45 mg pioglitazone daily for 3 years. After these 3 years, there was clinical improvement without adverse events.
Thanks. This is interesting stuff. I should have done research science as a major lol.
This is why I feel this drug is not worth its cost due to the change in lipid profile and potential for later in life coronary events. Its unfortunate the exactmechanisms remain unknown according to recent literature. Exercising in my mind its attenuating some of your risks, lets hope. It be interesting to see your response as a result of TZD use. I'd try for 3-6 months.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958563/
@Aaron76, do as you like. Your battle with this not mine. I am only providing perspective and a different point of view and a reminder that while I do hope you can tackle your pain, I do not feel there is a reasonable way to prove or at least rule out other variables in your case to make such assumptions. What you are doing could be affecting other mechanisms that may manifest as benefits or unintentional benefits or even potential harm that is not yet known while having no effect on what you intend... It's hard to know exactly what is happening, but hypothesizing is easy. That's where it gets dangerous. Everything comes at a cost. Just like these mentioned TZD's mentioned here - treat one problem but deal with the potential consequence of increased weight gain, hypertension and while the latest evidence says no increase in cardiovascular mortality by the RECORD trial there is some increased incidence in bladder cancer (Woo et al., 2020).
23 hours ago, k3tchup said:Thanks. This is interesting stuff. I should have done research science as a major lol.
This is why I feel this drug is not worth its cost due to the change in lipid profile and potential for later in life coronary events. Its unfortunate the exactmechanisms remain unknown according to recent literature. Exercising in my mind its attenuating some of your risks, lets hope. It be interesting to see your response as a result of TZD use. I'd try for 3-6 months.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958563/
@Aaron76, do as you like. Your battle with this not mine. I am only providing perspective and a different point of view and a reminder that while I do hope you can tackle your pain, I do not feel there is a reasonable way to prove or at least rule out other variables in your case to make such assumptions. What you are doing could be affecting other mechanisms that may manifest as benefits or unintentional benefits or even potential harm that is not yet known while having no effect on what you intend... It's hard to know exactly what is happening, but hypothesizing is easy. That's where it gets dangerous. Everything comes at a cost. Just like these mentioned TZD's mentioned here - treat one problem but deal with the potential consequence of increased weight gain, hypertension and while the latest evidence says no increase in cardiovascular mortality by the RECORD trial there is some increased incidence in bladder cancer (Woo et al., 2020).
I would like to try these TZD's but it's hard to get a prescrition if you don't have actual diabetes. I think it would also improve my hair quality that's suffered a lot. But as you said, there are also potential sides like bladder issues. ThoughI think it's safer than both accutane and finasteride.
@Gunnersuphow many hairs are you losing per day now?