Acne.org Products
On 11/21/2017 at 9:23 PM, TrueJustice said:Ok, a few things here,I absolutely knew this was coming from you, not in a bad way, I just know youre the champion in all things reporting!!
Ive reported my side effects/issues to so many doctors specialists etc Ive lost count, its actually now at the detriment of future employment- its on all my medical reports etc.
Secondly its too late to report to an FDA body for example side effects that started 20 years ago - thats coming from my GP!!!
Never heard of a statute of limitations on reporting a side effects. I was directed to use the FAERS system 12 years after developing side effects during a phone conversation with an FDA employee regarding the matter. Your GP might be giving you a cop-out response just because he doesn't feel like reporting it.
Never heard of post-Accutane being a detriment to employment either, unless you are too ill to perform the job because of it. What country do you live in where your employer is able to peruse medical records to find unrecognized medical conditions that you reported to your doctor? It's simple. Don't include it in information you provide when applying for, or accepting, employment or applying for insurance through your employer.
Hope you all are doing well. Great news about sexual side effects finally being added to the PIL for RoAccutane and generics in the UK! I am assuming that also includes all countries under the EMA's jurisdiction?
.
17 hours ago, Colinboko said:"Roche destroyed your lives - you can't change that. All you can do is stop them doing it to others"Now you're REALLY starting to piss me off. You have no idea what we're capable of discovering about this drug. What you said right there is a huge slap to guitarman and all his hard work. I'm not letting this drug destroy my life and I will help fight to find a way out of this. We have every right to be selfish and worry about ourselves right now. And by that I mean FOCUS ON WHAT IS IMPORTANT
Reporting sides doesn't do anything because no one listens!
I no longer comment on your post so please don't respond to mine!
Be as selfish as you like but ask yourself, why are you in this position!
9 hours ago, Dubya_B said:Never heard of a statute of limitations on reporting a side effects. I was directed to use the FAERS system 12 years after developing side effects during a phone conversation with an FDA employee regarding the matter. Your GP might be giving you a cop-out response just because he doesn't feel like reporting it.Never heard of post-Accutane being a detriment to employment either, unless you are too ill to perform the job because of it. What country do you live in where your employer is able to peruse medical records to find unrecognized medical conditions that you reported to your doctor? It's simple. Don't include it in information you provide when applying for, or accepting, employment or applying for insurance through your employer.
Hope you all are doing well. Great news about sexual side effects finally being added to the PIL for RoAccutane and generics in the UK! I am assuming that also includes all countries under the EMA's jurisdiction?
.
Hi Dubya, how you doing?
Yes, all of Europe I understand. Canada Health are up-dating and hopefully US and other countries will follow.
Everyone should bring this to the attention of the regulators in your own country because I suspect they won't automatically follow suit.
Dubya - I suspect they will downplay the sexual sides as rare and only temporary so I am trying to fight them on this but I don't
think it is a battle I will win.
This is why it would be so helpful if everyone wrote to MHRA with their case history and ask for a response and for their concerns to be recognised.
I know you were one of the guys who did email EMA(PRAC) so thank you so much.
Dysautonomia brought me this....
I think we have an acquired form of this that produces so many different symptoms. Moreover, we cannot detoxify. Not unlike the women who develop POTS after getting the Gardasil vaccine. High dose Thiamine has been recommended as a treatment.
Thiamine is needed for NADPH (the first step is isotretinoin catabolism) 60% comes from the pentose pathway
Thiamine is needed to produce stomach acid (think SIBO , bacterial imbalance, Chrons etc)
Thiamine is needed for collagen formation
Thiamine is needed to produce ATP (think ER dysfunction/ROS/detoxification)
Thiamine is needed for estrogen clearance in the liver (along with riboflavin) estrogen dominance, low T LH FSH etc.
Thiamine is needed to recycle GSH.
Thiamine is needed in steroid formation
Thiamine deficiency is noted in low ceruloplasmin results.
The test needed for this is an erythrocyte transketolase test. normal blood tests are not accurate.
ALLTHIAMINE is preferred. i have been using the topical. I tested high for estrogen last summer. I believe i had an estrogen-induced form of cholestasis. Ive had high bilirubin for 20 years since accutane. In the past 2 weeks, the whites of my eys have been totally clear, and ill be getting a confirming blood test. Taurine did this for a few days..but it was hit and miss. We could have downregulated receptors, and the full effect could take a while to fix. Magnesium and B1 should be taken together
Could accutane be the trigger like Gardisal?
something very very interesting here, and it related to P53 and FOX01
Bodo Melnik published something last month....
p53: key conductor of all anti-acne therapies
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606086/
This review based on translational research predicts that the transcription factor p53 is the key effector of all anti-acne therapies. All-trans retinoic acid (ATRA) and isotretinoin (13-cis retinoic acid) enhance p53 expression. Tetracyclines and macrolides via inhibiting p450 enzymes attenuate ATRA degradation, thereby increase p53. Benzoyl peroxide and hydrogen peroxide elicit oxidative stress, which upregulates p53. Azelaic acid leads to mitochondrial damage associated with increased release of reactive oxygen species inducing p53. p53 inhibits the expression of androgen receptor and IGF-1 receptor, and induces the expression of IGF binding protein 3. p53 induces FoxO1, FoxO3, p21 and sestrin 1, sestrin 2, and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), the key inducer of isotretinoin-mediated sebocyte apoptosis explaining isotretinoin™s sebum-suppressive effect. Anti-androgens attenuate the expression of miRNA-125b, a key negative regulator of p53. It can thus be concluded that all anti-acne therapies have a common mode of action, i.e., upregulation of the guardian of the genome p53. Immortalized p53-inactivated sebocyte cultures are unfortunate models for studying acne pathogenesis and treatment.
In contrast, an increased number of thiamine transporters are observed in cells that overexpress thiamine transport genes (mTHTR-1) and in cells that are exposed to conditions that induce DNA damage or p53 activation.56 Thiamine diphosphate inhibits p53 binding, and thiamine inhibits intracellular p53 activity.57 Thiamine treatment significantly decreases p53 expression in the cultured retinal neurons from diabetic rats.58 These observations suggest that the pro-apoptotic transcription factor p53 is activated by cellular damage in HIV infection and that thiamine ameliorates these effects.
Abstract
This review based on translational research predicts that the transcription factor p53 is the key effector of all anti-acne therapies. All-trans retinoic acid (ATRA) and isotretinoin (13-cis retinoic acid) enhance p53 expression. Tetracyclines and macrolides via inhibiting p450 enzymes attenuate ATRA degradation, thereby increase p53. Benzoyl peroxide and hydrogen peroxide elicit oxidative stress, which upregulates p53. Azelaic acid leads to mitochondrial damage associated with increased release of reactive oxygen species inducing p53. p53 inhibits the expression of androgen receptor and IGF-1 receptor, and induces the expression of IGF binding protein 3. p53 induces FoxO1, FoxO3, p21 and sestrin 1, sestrin 2, and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), the key inducer of isotretinoin-mediated sebocyte apoptosis explaining isotretinoin™s sebum-suppressive effect. Anti-androgens attenuate the expression of miRNA-125b, a key negative regulator of p53. It can thus be concluded that all anti-acne therapies have a common mode of action, i.e., upregulation of the guardian of the genome p53. Immortalized p53-inactivated sebocyte cultures are unfortunate models for studying acne pathogenesis and treatment.
Thiamine antagonists trigger p53-dependent apoptosis in differentiated SH-SY5Y cells
Abstract
This review based on translational research predicts that the transcription factor p53 is the key effector of all anti-acne therapies. All-trans retinoic acid (ATRA) and isotretinoin (13-cis retinoic acid) enhance p53 expression. Tetracyclines and macrolides via inhibiting p450 enzymes attenuate ATRA degradation, thereby increase p53. Benzoyl peroxide and hydrogen peroxide elicit oxidative stress, which upregulates p53. Azelaic acid leads to mitochondrial damage associated with increased release of reactive oxygen species inducing p53. p53 inhibits the expression of androgen receptor and IGF-1 receptor, and induces the expression of IGF binding protein 3. p53 induces FoxO1, FoxO3, p21 and sestrin 1, sestrin 2, and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), the key inducer of isotretinoin-mediated sebocyte apoptosis explaining isotretinoin™s sebum-suppressive effect. Anti-androgens attenuate the expression of miRNA-125b, a key negative regulator of p53. It can thus be concluded that all anti-acne therapies have a common mode of action, i.e., upregulation of the guardian of the genome p53. Immortalized p53-inactivated sebocyte cultures are unfortunate models for studying acne pathogenesis and treatment.
@tryingtohelp2014- good find! So you've improved your cholestasis symptoms with just thiamine & magnesium? What amounts? What about other symptoms, loss of libido etc, any improvements in this area?
Telling your doctor is one thing, but you don't think disclosing your mental health to a government entity (FDA) would affect your chances of joining the military or passing a govt ts security clearance? Interesting.
It's so unfair, because neurologists don't look at it like, "oh this chemical has damaged portions of your hippocampus or hypothalamus." It's more like well there's no proven link so we're gonna attribute other things in your life to your now compromised mental health,label you for everyone to see, and refer you to buy more pills from different pharma companies. Thanks medical industryfor all the help.
9 hours ago, tryingtohelp2014 said:Thiamine is needed for collagen formation
Also think eye floaters, a common occurrence for many of us
Im assuming you mean large amounts of Thiamine ( B1 ) as weve all taken this as part of our B complex supplements with very little effect yeah?
Ive even stepped it up a notch by taking the active form of Bs more recently but again nothing noticeable in the way I feel.
How much Thiamine do we need to be taking to notice anything?
I think Thiamine should be an essential part of our supplement cabinet. I will definitely introduce it to my supp stack. Nothing noticeable yet trialing Vitamin K or Lions Mane past couple days. Could be having a positive effect, but nothing that I can discern.
Vitamin C 1000mg and Thiamine should be mandatory daily. I only see benefits taking these. And the rest of my current stack is a few posts back if interested.
45 minutes ago, macleod said:I think Thiamine should be an essential part of our supplement cabinet. I will definitely introduce it to my supp stack. Nothing noticeable yet trialing Vitamin K or Lions Mane past couple days. Could be having a positive effect, but nothing that I can discern.
Vitamin C 1000mg and Thiamine should be mandatory daily. I only see benefits taking these. And the rest of my current stack is a few posts back if interested.
Taken by itself? Isn't there enough of it in say a B complex supplement pack?
I dunno, I just don't think running out and buying B1 is going to put me at an advantage over the active B complex pack I already have........unless someone can say otherwise?
13 hours ago, TrueJustice said:Im assuming you mean large amounts of Thiamine ( B1 ) as weve all taken this as part of our B complex supplements with very little effect yeah?
Ive even stepped it up a notch by taking the active form of Bs more recently but again nothing noticeable in the way I feel.
How much Thiamine do we need to be taking to notice anything?
up to 1500mg has been discussed. starting at a lower dose...and moving up. allthiaminecream is transdermal and gets around the whole digestive tract. it also crosses the blood brain barrier. this has been used successfully in autisticchildren. people have used both b complex andthiamine by itself read up on Dr Lonsdale. he is the expert in B1.
I think its a transporter problem..and you really need to saturate the serum.
some things you have to watch withthiamine... magnesium gets used up and folic acid.
I took Accutane about 10 years ago and I'm left with dry skin and dry red eyes (worst part) ever since. I do not really have any of the other common accutane side effects: suicide, depression, joint pains, constipation, hair loss, aches, etc..
I recently started taking Hyaluronic Acid capsules 1 week ago and haven't noticed any difference yet, although it's probably too early. I'm not sure if I have Vitamin A Toxicity?
Has anyone cured the red eye part? That's my biggest issue. What else should I try?
34 minutes ago, 08kx250f said:I took Accutane about 10 years ago and I'm left with dry skin and dry red eyes (worst part) ever since. I do not really have any of the other common accutane side effects: suicide, depression, joint pains, constipation, hair loss, aches, etc..
I recently started taking Hyaluronic Acid capsules 1 week ago and haven't noticed any difference yet, although it's probably too early. I'm not sure if I have Vitamin A Toxicity?
Has anyone cured the red eye part? That's my biggest issue. What else should I try?
start by reading through this thread
On 11/24/2017 at 3:30 AM, Justdry said:How many people take a vitamin A supplement or have a good amount of VItamin A in their diet?
And
How many of you have avoided it since taking accutane?
I've tried supplementing high dose Vitamin A on two different occasions. Negative effects are something that can creep on on you after awhile, sort of like Accutane. The first time on vitamin A I developed many more fine lines on my hands and hardened calluses at the base of my fingers. The second time gave me eye floaters that I still have to this day. There are also numerous supplements I've had negative reactions to, or as I've been looking at vitamin k2 processes, possibly antagonistic to. These days I don't avoid vitamin a, it's really not found in that high amount in most foods, (as retinoids) it's mostly in fortified milk and cereal.
On 11/23/2017 at 7:03 AM, hatetane said:Yes, all of Europe I understand. Canada Health are up-dating and hopefully US and other countries will follow.
Everyone should bring this to the attention of the regulators in your own country because I suspect they won't automatically follow suit.Dubya - I suspect they will downplay the sexual sides as rare and only temporary so I am trying to fight them on this but I don't
think it is a battle I will win.
This is why it would be so helpful if everyone wrote to MHRA with their case history and ask for a response and for their concerns to be recognised.I know you were one of the guys who did email EMA(PRAC) so thank you so much.
The battle to get sexual side effects listed has already been won and persistency of RoAccutane side effects is listed in the PIL already IIRC, even though "persistent sexual side effects" is not explicitly stated.
I think we actually won one of the battles for a change, thanks in part to your help.
NADPH ISOTRETINOINFINASTERIDE connection. we need to increase NADPH. 60% of our NADPH is made through the Thiamine dependant the pentose pathway.
Diagnostic use[edit]
Red blood celltransketolase activity is reduced in deficiency ofthiamine(vitamin B1), and may be used in the diagnosis ofWernicke's encephalopathyand other B1-deficiency syndromes if the diagnosis is in doubt.[8]Apart from the baseline enzyme activity (which may be normal even in deficiency states), acceleration of enzyme activity after the addition of thiamine pyrophosphate may be diagnostic of thiamine deficiency (0-15% normal, 15-25% deficiency, >25% severe deficiency).[9]
#1:Direct5-Alpha Reductase Inhibition
Competitive Inhibition
5-alpha reductase doesnt just arrive out of nowhere. In order for this enzyme to form and mediate the whole DHT conversion process, it needs the help of a coenzyme known as nicotinamide adenine dinucleotide phosphate or in other words,NADPH.
5-alpha reductase needs NADPH to convert free testosterone into DHT. Soan effective way tostopthe formation of 5-alpha reductase (and reducing DHT) is to
- Compete with the coenzyme NADPH, or
- Block NADPH
These are two mechanismsofdirect5-alpha reductase inhibition or for the lay person reducing 5-alpha reductase bystoppingit from forming.And while its still up for debate, the hair loss drugs Finasteride and Dutasteride two5-alpha reductase inhibitors appear to work in this way.
Mechanism 1: Compete With NADPH
Someresearchshows thatFinasteridecompeteswith the coenzyme NADPH. Finasterides moleculestake the place of NADPH in a cell, and in NADPHs absence, 5-alpha reductase cannot form. The end-result? Less DHT. And another 5-alpha reductase inhibiting drug Dutasteride seemsto dothe same thing (using a slightly different molecule).
Mechanism 2: Block NADPH (Or Bind To NADPHAnd Change ItsStructure)
Theres also research showing that instead of competing with NADPH,Finasteride may insteadbindto NADPHand change NADPHsstructure into adifferentcoenzyme one that doesnt support the formation of 5-alpha reductase. The bottom line: free testosterone can no longer convert into DHT.
Interestingly,zincmay also reduce 5-alpha reductase and througha similar manner. Evidence suggests thatzinc reduces NADPH production, thereby decreasing 5-alpha reductase activity.The less enzyme activity, the less DHT.
5 hours ago, tryingtohelp2014 said:NADPH ISOTRETINOINFINASTERIDE connection. we need to increase NADPH. 60% of our NADPH is made through the Thiamine dependant the pentose pathway.
Diagnostic use[edit]
Red blood celltransketolase activity is reduced in deficiency ofthiamine(vitamin B1), and may be used in the diagnosis ofWernicke's encephalopathyand other B1-deficiency syndromes if the diagnosis is in doubt.[8]Apart from the baseline enzyme activity (which may be normal even in deficiency states), acceleration of enzyme activity after the addition of thiamine pyrophosphate may be diagnostic of thiamine deficiency (0-15% normal, 15-25% deficiency, >25% severe deficiency).[9]
#1:Direct5-Alpha Reductase Inhibition
Competitive Inhibition
5-alpha reductase doesnt just arrive out of nowhere. In order for this enzyme to form and mediate the whole DHT conversion process, it needs the help of a coenzyme known as nicotinamide adenine dinucleotide phosphate or in other words,NADPH.
5-alpha reductase needs NADPH to convert free testosterone into DHT. Soan effective way tostopthe formation of 5-alpha reductase (and reducing DHT) is to
- Compete with the coenzyme NADPH, or
- Block NADPH
These are two mechanismsofdirect5-alpha reductase inhibition or for the lay person reducing 5-alpha reductase bystoppingit from forming.And while its still up for debate, the hair loss drugs Finasteride and Dutasteride two5-alpha reductase inhibitors appear to work in this way.
Mechanism 1: Compete With NADPH
Someresearchshows thatFinasteridecompeteswith the coenzyme NADPH. Finasterides moleculestake the place of NADPH in a cell, and in NADPHs absence, 5-alpha reductase cannot form. The end-result? Less DHT. And another 5-alpha reductase inhibiting drug Dutasteride seemsto dothe same thing (using a slightly different molecule).
Mechanism 2: Block NADPH (Or Bind To NADPHAnd Change ItsStructure)
Theres also research showing that instead of competing with NADPH,Finasteride may insteadbindto NADPHand change NADPHsstructure into adifferentcoenzyme one that doesnt support the formation of 5-alpha reductase. The bottom line: free testosterone can no longer convert into DHT.
Interestingly,zincmay also reduce 5-alpha reductase and througha similar manner. Evidence suggests thatzinc reduces NADPH production, thereby decreasing 5-alpha reductase activity.The less enzyme activity, the less DHT.
I read on a propeciahelp thread that isotretinoin isn't a permanently binding 5ari like finasteride. Do you think that's true?
Hello everyone!
Been following this thread for the last few years as me myself also have been suffering from the lasting side effects from isotretinoin, and I feel you all. I feel better today, much because of healthy food and exercise, but I'm not fully recovered.
It is much because of this that I chose to become a doctor, and I have now been studying medicine for almost 1 year. I recently found out about a quite new method of determining if you have been suffering from a lot of oxidative stress to DNA (DNA mutations). This method is known as 8-Oxoguanine testing, which is a urine test where they scan your urine for 8-Oxoguanine. If you have more than normal amount of these molecules in the urine, it means that you have been suffering from oxidative stress to your DNA.
My hypothesis is that Isotretinoin damages DNA, and that is why we have to deal with these long lasting side effects.
However, as of right now these tests are rarely performed on a regular hospital, because the method is still very new. So you probably need to find a specialized lab to do it. I would have loved to do this test on myself, but right now I don't have the time or know any place around here that performs it.
If anyone of you would find this interesting and could find a place to do such a test - I would love to hear about your results!
A proof that accutane causes DNA damages could be the end of this drug.
@tryingtohelp The wikipedia article on NADPH mentions isotretinoin https://en.wikipedia.org/wiki/Retinol_dehydrogenase
This article on depression and Isotretinoin also mentions NADPH http://forums.phoenixrising.me/index.php?threads/roaccutane-caused-depression-isotretinoin.12117/
NADPH is also mentioned in relation to birth defects in a study with rats http://www.ejh.it/index.php/ejh/article/view/ejh.2012.e50/2491
3 hours ago, draci said:@tryingtohelp The wikipedia article on NADPH mentions isotretinoin https://en.wikipedia.org/wiki/Retinol_dehydrogenase
This article on depression and Isotretinoin also mentions NADPH http://forums.phoenixrising.me/index.php?threads/roaccutane-caused-depression-isotretinoin.12117/
NADPH is also mentioned in relation to birth defects in a study with rats http://www.ejh.it/index.php/ejh/article/view/ejh.2012.e50/2491
the CYP26A enzyme responsible more than any other in detoxifying excess ATRA (which isotretinoin gets isomerized to in the body) is NADPH dependent.
4 hours ago, RandomInternetdude said:Hello everyone!
Been following this thread for the last few years as me myself also have been suffering from the lasting side effects from isotretinoin, and I feel you all. I feel better today, much because of healthy food and exercise, but I'm not fully recovered.
It is much because of this that I chose to become a doctor, and I have now been studying medicine for almost 1 year. I recently found out about a quite new method of determining if you have been suffering from a lot of oxidative stress to DNA (DNA mutations). This method is known as 8-Oxoguanine testing, which is a urine test where they scan your urine for 8-Oxoguanine. If you have more than normal amount of these molecules in the urine, it means that you have been suffering from oxidative stress to your DNA.
My hypothesis is that Isotretinoin damages DNA, and that is why we have to deal with these long lasting side effects.
However, as of right now these tests are rarely performed on a regular hospital, because the method is still very new. So you probably need to find a specialized lab to do it. I would have loved to do this test on myself, but right now I don't have the time or know any place around here that performs it.
If anyone of you would find this interesting and could find a place to do such a test - I would love to hear about your results!
A proof that accutane causes DNA damages could be the end of this drug.
Yeah but what happens after the test?? What would they put you on for example?
Anything different to what were experimenting with now?