Acne.org Products
18 hours ago, under_tow said:The theory/hypothesis is overload with beta-carotene, and it cascades out of control, meaning increased retinol -> retinoic acid. You end up in VA overload.
Few people on Grant's forum have DNA tested positive for this scenario using 23andMe. This happens without accutane, and most likely what happened to all us pre-accutane. We were all messed up before we took accutane, accutane just makes the VA overload worse.
So you thinking the mutation makes you overloaded not deficient?
2 hours ago, Calcified said:So you thinking the mutation makes you overloaded not deficient?
Yep the hypothesis is you become a super-converter of beta carotene, when carotene cleaves you get two retinols.
Studies have shown that the liver can hold about 2 years worth of vitamin A, when zero VA is coming in. I suspect anyone with acne has two years worth of retins stored in their liver, and all the dietary vitamin A coming in after storage is full, starts the cascade to auto-immunes, acne, etc... Being a beta-carotene super converter would help this process along even quicker. Then us folks with this situation, throw accutane jet fuel on the fire.
I am still seeing improvement at now over 6 months VA free. I think it will probably take 2yrs for full remission, getting the VA out is a excruciating long process, especially after high dose retinoic acid. Would be nice to have a simple VA chelator to test this quicker.
30 minutes ago, under_tow said:Yep the hypothesis is you become a super-converter of beta carotene, when carotene cleaves you get two retinols.
Studies have shown that the liver can hold about 2 years worth of vitamin A, when zero VA is coming in. I suspect anyone with acne has two years worth of retins stored in their liver, and all the dietary vitamin A coming in after storage is full, starts the cascade to auto-immunes, acne, etc... Being a beta-carotene super converter would help this process along even quicker. Then us folks with this situation, throw accutane jet fuel on the fire.
I am still seeing improvement at now over 6 months VA free. I think it will probably take 2yrs for full remission, getting the VA out is a excruciating long process, especially after high dose retinoic acid. Would be nice to have a simple VA chelator to test this quicker.
I have stopped the palmitate and am on the zinc but I'm getting some acne now which has surprised me, but I feel like my androgen levels have improved. My digestion still good after palmitate so it helped with that, no longer stomach pains after meals. My blood glucose also went down, so it must have improved my insulin sensitivity.
Also i recently got confirmation in writing, they say I have isotretinoin induced dish disease.
43 minutes ago, Calcified said:Also i recently got confirmation in writing, they say I have isotretinoin induced dish disease.
That sucks, but makes sense, calcium is leeched from bone and teeth to buffer the acidity of retinoic acid, that free calcium is dumped into the soft tissues, accutane loves the cartilage, ligaments, tendons...
Some studies show that palmitate is actively turned to 13-cis-retinoic (accutane) before it is excreted, so it is going to have accutane like side effects, that most likely would contribute to the ligament problem. Problem good you have stopped it.
Circulating Endogenous Retinoic Acid Concentrations among Participants Enrolled in a Randomized Placebo-Controlled Clinical Trial of Retinyl Palmitate: http://cebp.aacrjournals.org/content/cebp/13/11/1687.full.pdf
But all trans retinoic acid is not the storage form of Vitamin A. Its an active metabolite.
Do we have some evidence of long term storage of Retinoic acid Specifically?
Isotretinoinand theliver. Unlike vitamin A,isotretinoin is not stored in the liver.Isotretinoinis probablynotdirectly hepatotoxic.
Oral isotretinoin - NPS MedicineWise
https://www.nps.org.au/australian-prescriber/articles/oral-isotretinoin
In foods of animal origin, the major form of vitamin A is anester, primarilyretinyl palmitate, which is converted toretinol(chemically analcohol) in thesmall intestine. The retinol form functions as a storage form of the vitamin, and can be converted to and from its visually activealdehydeform,retinal.
All-trans-retinoic acid can be produced in the body by two sequential oxidation steps that convert all-trans-retinol to retinaldehyde to all-trans-retinoic acid, but once produced it cannot be reduced again to all-trans-retinol. The enzymes that generate retinoic acid for control of gene expression includeretinol dehydrogenase(i.e. Rdh10) that metabolizes retinol to retinaldehyde, and three types ofretinaldehyde dehydrogenase, i.e. RALDH1 (ALDH1A1), RALDH2 (ALDH1A2), and RALDH3 (ALDH1A3)[8]that metabolize retinaldehyde to retinoic acid.[2]Enzymes that metabolize excess all-trans-retinol to prevent toxicity includealcohol dehydrogenaseandcytochrome P450(cyp26).[9]
All-trans-retinoic acid function in the absence of precursors all-trans-retinol or retinaldehyde[edit]
All-trans-retinoic acid is responsible for most of the activity of vitamin A1, save visual pigment effects that requireretinal(retinaldehyde), and cell metabolism effects that may requireretinolitself. Also, some biochemical functions necessary for fertility in vitamin A deficient male and female mammals originally appeared to require all-trans-retinol for rescue, but this is due to a requirement for local conversion of all-trans-retinol to all-trans-retinoic acid, as administered all-trans-retinoic acid does not reach some critical tissues unless given in high amounts. Thus, if animals are fed only all-trans-retinoic acid but no vitamin A1(all-trans-retinol or retinal), they suffer none of the growth-stunting or epithelial-damaging effects of lack of vitamin A1(including noxerophthalmiadryness of the cornea). They do suffer retina degeneration and blindness, due toretinal(retinaldehyde) deficiency.
In addition, vitamin A1-deprived but all-trans-retinoic acid-supplemented male rats exhibithypogonadismandinfertilitydue to lack of local retinoic acid synthesis in the testis; similar treatment of female rats causes infertility due tofetal resorptioncaused by a lack of local retinoic acid synthesis in the embryo.[10][11]The retinoic acid synthesis in testes is catalyzed primarily by the RALDH2 (ALDH1A2) aldehyde dehydrogenase. Suppressing this enzyme has been proposed as a possible way to make a male contraceptive pill, because retinoic acid is necessary forspermatogenesisin humans, much as in rats
Not to say there couldn't be clues or ongoing issues based on its metabolism.
Example
Retinoic acid metabolism blocking agents (RAMBAs) for treatment of cancer and dermatological diseases.
ATRA has been used successfully in differentiated therapy of acute promyelocytic leukemia, skin cancer, Kaposi's sarcoma, and cutaneous T-cell lymphoma, and also in the treatment of acne and psoriasis. However, its usefulness is limited by the rapid emergence of acquired ATRA resistance involving multifactoral mechanisms. A key mechanism of resistance involves ATRA-induced catabolism of ATRA. Thus, a novel strategy to overcome the limitation associated with exogenous ATRA therapy has been to modulate and/or increase the levels of endogenous ATRA by inhibiting the cytochrome P450-dependent ATRA-4-hydroxylase enzymes (particularly CYP26s) responsible for ATRA metabolism. These inhibitors are also referred to as retinoic acid metabolism blocking agents (RAMBAs)
1 hour ago, guitarman01 said:But all trans retinoic acid is not the storage form of Vitamin A. Its an active metabolite.
Do we have some evidence of long term storage of Retinoic acid Specifically?
Isotretinoinand theliver. Unlike vitamin A,isotretinoin is not stored in the liver.Isotretinoinis probablynotdirectly hepatotoxic.
Oral isotretinoin - NPS MedicineWise
https://www.nps.org.au/australian-prescriber/articles/oral-isotretinoin
Unlike vitamin A,isotretinoin is not stored in the liverand is not associated with many of the toxic effects of high dose vitamin A therapy. Its mechanism of action...
In foods of animal origin, the major form of vitamin A is anester, primarilyretinyl palmitate, which is converted toretinol(chemically analcohol) in thesmall intestine. The retinol form functions as a storage form of the vitamin, and can be converted to and from its visually activealdehydeform,retinal.
All-trans-retinoic acid can be produced in the body by two sequential oxidation steps that convert all-trans-retinol to retinaldehyde to all-trans-retinoic acid, but once produced it cannot be reduced again to all-trans-retinol. The enzymes that generate retinoic acid for control of gene expression includeretinol dehydrogenase(i.e. Rdh10) that metabolizes retinol to retinaldehyde, and three types ofretinaldehyde dehydrogenase, i.e. RALDH1 (ALDH1A1), RALDH2 (ALDH1A2), and RALDH3 (ALDH1A3)[8]that metabolize retinaldehyde to retinoic acid.[2]Enzymes that metabolize excess all-trans-retinol to prevent toxicity includealcohol dehydrogenaseandcytochrome P450(cyp26).[9]
All-trans-retinoic acid function in the absence of precursors all-trans-retinol or retinaldehyde[edit]
All-trans-retinoic acid is responsible for most of the activity of vitamin A1, save visual pigment effects that requireretinal(retinaldehyde), and cell metabolism effects that may requireretinolitself. Also, some biochemical functions necessary for fertility in vitamin A deficient male and female mammals originally appeared to require all-trans-retinol for rescue, but this is due to a requirement for local conversion of all-trans-retinol to all-trans-retinoic acid, as administered all-trans-retinoic acid does not reach some critical tissues unless given in high amounts. Thus, if animals are fed only all-trans-retinoic acid but no vitamin A1(all-trans-retinol or retinal), they suffer none of the growth-stunting or epithelial-damaging effects of lack of vitamin A1(including noxerophthalmiadryness of the cornea). They do suffer retina degeneration and blindness, due toretinal(retinaldehyde) deficiency.
In addition, vitamin A1-deprived but all-trans-retinoic acid-supplemented male rats exhibithypogonadismandinfertilitydue to lack of local retinoic acid synthesis in the testis; similar treatment of female rats causes infertility due tofetal resorptioncaused by a lack of local retinoic acid synthesis in the embryo.[10][11]The retinoic acid synthesis in testes is catalyzed primarily by the RALDH2 (ALDH1A2) aldehyde dehydrogenase. Suppressing this enzyme has been proposed as a possible way to make a male contraceptive pill, because retinoic acid is necessary forspermatogenesisin humans, much as in rats
Not to say there couldn't be clues or ongoing issues based on its metabolism.
Example
Retinoic acid metabolism blocking agents (RAMBAs) for treatment of cancer and dermatological diseases.
ATRA has been used successfully in differentiated therapy of acute promyelocytic leukemia, skin cancer, Kaposi's sarcoma, and cutaneous T-cell lymphoma, and also in the treatment of acne and psoriasis. However, its usefulness is limited by the rapid emergence of acquired ATRA resistance involving multifactoral mechanisms. A key mechanism of resistance involves ATRA-induced catabolism of ATRA. Thus, a novel strategy to overcome the limitation associated with exogenous ATRA therapy has been to modulate and/or increase the levels of endogenous ATRA by inhibiting the cytochrome P450-dependent ATRA-4-hydroxylase enzymes (particularly CYP26s) responsible for ATRA metabolism. These inhibitors are also referred to as retinoic acid metabolism blocking agents (RAMBAs)
Yes retinoic acid is not back converted to retinol or retinyl, and all that retinoic acid isn't going to be excreted quickly, so the dosage that we take in accutane prescription gets to do a lot of damage. All beta-carotene and retins, need to be converted to RA to excrete. So accutane is on top of all the retins stored already in the liver, fat tissues, and beta carotene throughout the body, which takes years to get down. Would create a nice bottleneck. Body is smart though, studies show the fuller our liver is of vitamin A, the quicker it ramps up excretion, but still takes years to deplete it down.
Anyone able to find studies on retinoic acid excretion rates, not funded by Roche.
The only food that doesn't have carotenoids or preformed A is rice. All diets are loaded with VA.
1 hour ago, under_tow said:So accutane is on top of all the retins stored already in the liver, fat tissues, and beta carotene throughout the body, which takes years to get down.
Evidence pls?
6 hours ago, guitarman01 said:But all trans retinoic acid is not the storage form of Vitamin A. Its an active metabolite.
Do we have some evidence of long term storage of Retinoic acid Specifically?
Isotretinoinand theliver. Unlike vitamin A,isotretinoin is not stored in the liver.Isotretinoinis probablynotdirectly hepatotoxic.
Oral isotretinoin - NPS MedicineWise
https://www.nps.org.au/australian-prescriber/articles/oral-isotretinoin
Unlike vitamin A,isotretinoin is not stored in the liverand is not associated with many of the toxic effects of high dose vitamin A therapy. Its mechanism of action...
In foods of animal origin, the major form of vitamin A is anester, primarilyretinyl palmitate, which is converted toretinol(chemically analcohol) in thesmall intestine. The retinol form functions as a storage form of the vitamin, and can be converted to and from its visually activealdehydeform,retinal.
All-trans-retinoic acid can be produced in the body by two sequential oxidation steps that convert all-trans-retinol to retinaldehyde to all-trans-retinoic acid, but once produced it cannot be reduced again to all-trans-retinol. The enzymes that generate retinoic acid for control of gene expression includeretinol dehydrogenase(i.e. Rdh10) that metabolizes retinol to retinaldehyde, and three types ofretinaldehyde dehydrogenase, i.e. RALDH1 (ALDH1A1), RALDH2 (ALDH1A2), and RALDH3 (ALDH1A3)[8]that metabolize retinaldehyde to retinoic acid.[2]Enzymes that metabolize excess all-trans-retinol to prevent toxicity includealcohol dehydrogenaseandcytochrome P450(cyp26).[9]
All-trans-retinoic acid function in the absence of precursors all-trans-retinol or retinaldehyde[edit]
All-trans-retinoic acid is responsible for most of the activity of vitamin A1, save visual pigment effects that requireretinal(retinaldehyde), and cell metabolism effects that may requireretinolitself. Also, some biochemical functions necessary for fertility in vitamin A deficient male and female mammals originally appeared to require all-trans-retinol for rescue, but this is due to a requirement for local conversion of all-trans-retinol to all-trans-retinoic acid, as administered all-trans-retinoic acid does not reach some critical tissues unless given in high amounts. Thus, if animals are fed only all-trans-retinoic acid but no vitamin A1(all-trans-retinol or retinal), they suffer none of the growth-stunting or epithelial-damaging effects of lack of vitamin A1(including noxerophthalmiadryness of the cornea). They do suffer retina degeneration and blindness, due toretinal(retinaldehyde) deficiency.
In addition, vitamin A1-deprived but all-trans-retinoic acid-supplemented male rats exhibithypogonadismandinfertilitydue to lack of local retinoic acid synthesis in the testis; similar treatment of female rats causes infertility due tofetal resorptioncaused by a lack of local retinoic acid synthesis in the embryo.[10][11]The retinoic acid synthesis in testes is catalyzed primarily by the RALDH2 (ALDH1A2) aldehyde dehydrogenase. Suppressing this enzyme has been proposed as a possible way to make a male contraceptive pill, because retinoic acid is necessary forspermatogenesisin humans, much as in rats
Not to say there couldn't be clues or ongoing issues based on its metabolism.
Example
Retinoic acid metabolism blocking agents (RAMBAs) for treatment of cancer and dermatological diseases.
ATRA has been used successfully in differentiated therapy of acute promyelocytic leukemia, skin cancer, Kaposi's sarcoma, and cutaneous T-cell lymphoma, and also in the treatment of acne and psoriasis. However, its usefulness is limited by the rapid emergence of acquired ATRA resistance involving multifactoral mechanisms. A key mechanism of resistance involves ATRA-induced catabolism of ATRA. Thus, a novel strategy to overcome the limitation associated with exogenous ATRA therapy has been to modulate and/or increase the levels of endogenous ATRA by inhibiting the cytochrome P450-dependent ATRA-4-hydroxylase enzymes (particularly CYP26s) responsible for ATRA metabolism. These inhibitors are also referred to as retinoic acid metabolism blocking agents (RAMBAs)
This is what I always think about, developed resistance, they say it doesn't happen with 13 CIS but maybe it does, years later?
14 hours ago, under_tow said:That sucks, but makes sense, calcium is leeched from bone and teeth to buffer the acidity of retinoic acid, that free calcium is dumped into the soft tissues, accutane loves the cartilage, ligaments, tendons...
Some studies show that palmitate is actively turned to 13-cis-retinoic (accutane) before it is excreted, so it is going to have accutane like side effects, that most likely would contribute to the ligament problem. Problem good you have stopped it.
Circulating Endogenous Retinoic Acid Concentrations among Participants Enrolled in a Randomized Placebo-Controlled Clinical Trial of Retinyl Palmitate: http://cebp.aacrjournals.org/content/cebp/13/11/1687.full.pdf
I read this study before and it does raise 13 CIS but it also doesn't jump the conversion process or the other retinoic acids. I only got up to about 50,000iu a day, lips got a bit drier but nothing like accutane.
If you could find some evidence of long term storage of retinoic acid that would be great.
I have a study here showing tissue accumulation from circulating retinoic acid from plasma, but it gets metabolized on a cellular level so rapidly from multiple body sites, they had to sacrifice the rats immediately after dosing.
It also goes on to state what I last posted, a person could actually become vitamin a deficient, even if they maintained high retinoic acid levels.
Plasma Delivery of Retinoic Acid to Tissues in the Rat
http://www.jbc.org/content/270/30/17850.long
Our studies investigated the extent to which plasma all-trans-RA contributes to tissue pools of this retinoid
In preliminary experiments developing and characterizing the methodologies used for our studies, it quickly became obvious that plasma retinoic acid was being taken up by most tissues and was very rapidly being metabolized. We observed that after the stoppage of the circulation of a perfused rat (i.e.upon sacrifice) the metabolism of retinoic acid by tissues continued. Thus, a critical point in the design of these experiments was to allow very little time to elapse between the stoppage of circulation and the dissection of tissues. This ensured that our measures provided accurate estimations of the contribution which plasma retinoic acid makes to tissue pools. With this in mind and as part of our experimental design, we limited the maximum period of time between stoppage of the circulation and flash freezing of the final dissected tissue to 5 min.
The literature indicates that plasma and tissue retinol turns over in the rat at a much slower rate than retinoic acid(34,35). If the average tissue concentration of all-trans-retinoic acid is taken as 4 ng/g (seeTable 1), this would mean that 2000 ng of all-trans-retinoic acid is present in the entire body of a 500-g rat. Since the ACR for all-trans-retinoic acid is 192 ng/h, this indicates that, for control rats, the whole body pool of all-trans-retinoic acid is replaced approximately once every 10 h.
retinoid nutritional status was found to influence the rate of retinoic acid but not the rate of oleic acid clearance from the plasma. Overall, these data suggest that retinoic acid accumulation by cells and tissues occurs through processes which are tissue and cell type specific and which are responsive to physiologic (e.g.nutritional) state.
A striking finding of our studies was that the testis, which possesses all-trans-retinoic acid at a level similar to the other tissues (seeTable 1), derives almost none of this retinoid from the circulation. Since 1925, it has been known that a rat maintained in the total absence of dietary retinol, but supplemented with all-trans-retinoic acid in the diet, will be generally healthy, but blind and sterile(1,38). Because retinaldehyde is the active retinoid in the visual cycle and since all-trans-retinoic acid cannot be reduced to retinaldehyde, the inability of dietary supplementation with all-trans-retinoic acid to restore vision is understood (39). It is known that the lesion in reproduction arises from a failure of spermatogenesis, which shows an obligatory requirement for retinol in the diet. However, the biochemical basis for the inability of all-trans-retinoic acid to substitute for the obligatory retinol needed during spermatogenesis has not been understood. A recent study indicated that when a large dose of all-trans-retinoic acid (5 mg) was injected intratesticularly into a retinoid-deficient rat in which spermatogenesis was blocked, spermatogenesis rapidly resumed(40). This suggests that retinoic acid can promote spermatogenesis. Our data indicate that a barrier exists in the testis for the uptake of all-trans-retinoic acid from the circulation. This would explain why dietary all-trans-retinoic acid cannot substitute for retinol to maintain spermatogenesis
to add to this 13 cis selectively converts to all trans retinoic acid in tissues. 13 cis does not induce the p450 enzymes involved in xenobiotic metabolism, thus grants the higher potency.13 cis has effects separate from either 9 cis and all trans. It is still considered a natural substance, but maybe 13 cis has the potential to be more toxic.
13-cis-retinoic acid metabolism in vivo. The major tissue metabolites in the rat have the all-trans configuration.
Guitarman01 - so you saying accutane could of converted to alot of all trans in tissue, so one could now have all trans resistance/deficiency ?
What I'm starting to think is vitamin a is good and derivatives is bad.
Is that why so many have erection problems? Retinol to acid is not working right?
Retinaldehyde is that the missing link?
I think I read retinaldehyde is anti bacterial so maybe that's why I get folliculitis? But you there expert on bacteria not me.
4 hours ago, Calcified said:Guitarman01 - so you saying accutane could of converted to alot of all trans in tissue, so one could now have all trans resistance/deficiency ?
"ATRA has been used successfully in differentiated therapy of acute promyelocytic leukemia, skin cancer, Kaposi's sarcoma, and cutaneous T-cell lymphoma, and also in the treatment of acne and psoriasis. However, its usefulness is limited by the rapid emergence of acquired ATRA resistance involving multifactorialmechanisms."
Its saying ATRA became ineffective. Which would have been good in our case.
A few more things.
"the rapid emergence of acquired ATRA resistance"
When I see this, I almost start to think bacterial resistance, similar to antibiotic resistance.
13-cis is actually a biologically inactive form of vitamin a that does not attach to receptors, its potencyseems to be in its conversion to all-trans retinoic acid in tissues.
Drug Metabolism by the Host and Gut Microbiota: A Partnership or Rivalry?
not only does our liver contain p450 enzymes involved in the process of metabolizing drugs, so do many microbes
https://www.ncbi.nlm.nih.gov/pubmed/26261284
The importance of the gut microbiome in determining not only overall health, but also in the metabolism of drugs and xenobiotics, is rapidly emerging. It is becoming increasingly clear that the gut microbiota can act in concert with the host cells to maintain intestinal homeostasis, cometabolize drugs and xenobiotics, and alter the expression levels of drug-metabolizing enzymes and transporters and the expression and activity levels of nuclear receptors. In this myriad of activities, the impact of the microbiota may be beneficial or detrimental to the host.
Microbes can metabolize compounds to either make less/more toxicor ineffective.
They can also prolong drug circulation by using glucuronidation as a carbon source, so a drug meant to be excreted, gets put back into circulation.
The main source ofretinoic acid that contributes to circulating retinoic acidalso seems to be the intestines, not the liver.
That's discussion of secondary and tertiary sources. Not evidence.
I've been destroyed for 20 years since Accutane and on a rather low vitamin A diet for most of those 20 years. Not intentionally, that was simply how I ate. I actually began eating more foods rich with Vit A around 2010 and it made no difference. Began screwing with supplements to fix this and THAT is when this began getting worse fast. I was relatively fine after my long first Course of Accutane and crashed hard after a couple weeks on a second course.
As someone else mentioned, there are people who have post-Accutane health issues for years after only a handful of pills, others are completely fine after many high-dose courses.
If Generaux was right about retinol and RA being poisonous, people who have been eating eggs, fish, spinach and butter all their lives would all be severely ill.
Sort of pissed off that post-Accutane patients are getting dragged into some idiotic conspiracy theory and wacky "treatment protocol" that won't work, yet again, instead of banding together for serious research.
Edit- Is Grant Genereux even the source of this information about moderate amounts of vit A being poisonous and linking this with post-Accutane Syndrome, or is someone taking his recommendations for lowering the standard of what is considered a toxic dietary intake and getting carried away with it?
On 5/19/2019 at 5:13 PM, trak said:I don't understand the direction of your discussion, because me and other people, got sexual sides just after single dose.
Permanent side effects from just 1 pill is pretty hard to understand. Most of the general population isnt affected in such a way. A Dr would vehemently deny Accutane being the long term cause. If such a thing happened to me after just 1 pill, im not sure if I would entirely point the finger at Accutane, but maybe something that I was already predisposed to, that Accutane brought to light.
Of Course Ibelieve you, but being affected in such a way after such a limited dosage of a natural substance, I would be looking at this as a whole health issue.Why was I more susceptive? Maybe a person would have been to Propecia, SSRI's, or Antibiotics as well.
Speaking of antibiotics, a single dose has shown to be effective. So maybe you can find a correlation here for a long term effect?
So something flipped a switch? upregulated? Downregulated? Accutane seems alot more complicated than just androgen suppression, it doesn't explain everything it's capable of.
Im looking at how Accutane might be metabolised, especially when more and more information is becoming available on the subject. This is seperate from say long term storage after a 20 year period in multiple tissue sites. IF there was some research to back this notion up though, im all for it. A person has permanent ed or complete loss of function or sensitivity, I also had permanent hair shedding that never came back. Is that a one and done thing or is there still an ongoing issue that needs to be solved? For me its been progressive.
Did anyone see the Victoria Derbyshire show UK bbc2 can been see on catch up.
You can read about it online :Victoria Derbyshire.
Anyone from the UK interested in a group legal case?
Anyone interested in raising awareness?
Is anyone prepared to share a case history in order educate?
Please contact me.
On 6/7/2017 at 1:34 AM, hatetane said:Just checking to make sure you know not to take ant SSRI'S I am begging you guys to send an email highlighting your side effects and how this drug has affected your lives.
The review is going on right now!
One group email will take no more than 20 minutes.Please, please please - we can't keep letting kids die!
[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];@ima.is" rel="" style="text-decoration:underline;font-style:normal;font-weight:normal;letter-spacing:normal;text-indent:0px;text-transform:none;font-family:Calibri, sans-serif, serif, EmojiFont;font-size:14.6667px">hrefna.gudmundsdottir@ima.is;[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];[email protected];@ms.etat.lu" rel="" style="text-decoration:underline;font-style:normal;font-weight:normal;letter-spacing:normal;text-indent:0px;text-transform:none;font-family:Calibri, sans-serif, serif, EmojiFont;font-size:14.6667px">Marcel.Bruch@ms.etat.lu;[email protected];[email protected];[email protected];[email protected];[email protected];@noma.no" rel="" style="text-decoration:underline;font-style:normal;font-weight:normal;letter-spacing:normal;text-indent:0px;text-transform:none;font-family:Calibri, sans-serif, serif, EmojiFont;font-size:14.6667px">helgahaugom.olsen@noma.no;@noma.no" rel="" style="text-decoration:underline;font-style:normal;font-weight:normal;letter-spacing:normal;text-indent:0px;text-transform:none;font-family:Calibri, sans-serif, serif, EmojiFont;font-size:14.6667px">kristin.kvande@noma.no;[email protected];[email protected];[email protected];[email protected];@anm.ro" rel="" style="text-decoration:underline;font-style:normal;font-weight:normal;letter-spacing:normal;text-indent:0px;text-transform:none;font-family:Calibri, sans-serif, serif, EmojiFont;font-size:14.6667px">roxana.stroe@anm.ro;@anm.ro" rel="" style="text-decoration:underline;font-style:normal;font-weight:normal;letter-spacing:normal;text-indent:0px;text-transform:none;font-family:Calibri, sans-serif, serif, EmojiFont;font-size:14.6667px">nicolae.fotin@anm.ro;[email protected];[email protected];[email protected];[email protected];[email protected];@mpa.se" rel="" style="text-decoration:underline;font-style:normal;font-weight:normal;letter-spacing:normal;text-indent:0px;text-transform:none;font-family:Calibri, sans-serif, serif, EmojiFont;font-size:14.6667px">HPHARMACOVIGILANCE@mpa.se;[email protected];[email protected];[email protected];[email protected];[email protected];@pei.de" rel="" style="text-decoration:underline;font-style:normal;font-weight:normal;letter-spacing:normal;text-indent:0px;text-transform:none;font-family:Calibri, sans-serif, serif, EmojiFont;font-size:14.6667px">Brigitte.Keller-Stanislawski@pei.de;[email protected];[email protected];[email protected];[email protected];[email protected];@online.no" rel="" style="text-decoration:underline;font-style:normal;font-weight:normal;letter-spacing:normal;text-indent:0px;text-transform:none;font-family:Calibri, sans-serif, serif, EmojiFont;font-size:14.6667px">myhr@online.no
Has anyone reported their side effects recently?
https://yellowcard.mhra.gov.uk/
I also have a contact at MHRA if anyone wants to share their whole story which would be a really good thing.
We need everyone to report their side effects.
PM me for more info?
1 hour ago, guitarman01 said:Permanent side effects from just 1 pill is pretty hard to understand. Most of the general population isnt affected in such a way. A Dr would vehemently deny Accutane being the long term cause. If such a thing happened to me after just 1 pill, im not sure if I would entirely point the finger at Accutane, but maybe something that I was already predisposed to, that Accutane brought to light.
Of Course Ibelieve you, but being affected in such a way after such a limited dosage of a natural substance, I would be looking at this as a whole health issue.Why was I more susceptive? Maybe a person would have been to Propecia, SSRI's, or Antibiotics as well.
Speaking of antibiotics, a single dose has shown to be effective. So maybe you can find a correlation here for a long term effect?
So something flipped a switch? upregulated? Downregulated? Accutane seems alot more complicated than just androgen suppression, it doesn't explain everything it's capable of.
Im looking at how Accutane might be metabolised, especially when more and more information is becoming available on the subject. This is seperate from say long term storage after a 20 year period in multiple tissue sites. IF there was some research to back this notion up though, im all for it. A person has permanent ed or complete loss of function or sensitivity, I also had permanent hair shedding that never came back. Is that a one and done thing or is there still an ongoing issue that needs to be solved? For me its been progressive.
Crank only took for 10 days. You can see his posts if you go back to when this thread first started. I met Crank personally and he is the most credible guy you could me and now a med student. He was about 20 when he too Roaccutane - he is not a campaigner, he just wants to get better. We know sexual sides are not rare but having bad sides after a few days probably is. Nonetheless the drug is lethal and shows that everyone who takes is is taking huge risks. The perception that as long as you are monitored you will be safe is a misguided one and it is putting patients at risk. Once the damage is done there is no turning back.
If you guys don't share your experiences with your dermatologists how are they suppose to know this?
Tell your dermatologists and your GP's and insist that they record and report it to the regulators and the pharmaceutical companies.
If the millions of victims had done this years ago prob none of you would be suffering to day.
By keeping silent you are letting Roche win - they are making millions at your expense.
22 hours ago, hatetane said:Did anyone see the Victoria Derbyshire show UK bbc2 can been see on catch up.
You can read about it online :Victoria Derbyshire.
im not able to watch it from the us apparently. i did see the article. what was the thing on younger people getting bowel cancer?
was that a separate story?
I can understand a 10 day course having more potential to do damage. i guess another point is though is thatid like my chances of resolution alot more taking 1 or 10 pills as opposed to 120.
as far as millions of sufferers, its probably the other way around just looking at alot of pro accutane feedback from that story.
how many people have graced these pages? maybe hundreds?not even a 1000? what is there like 5 of us on here right now?
i know the lifelong potential to do damage is there, but we seem to be a small minority. it doesn't make it right of course or a campaign to be ignored.
Hard to believe this is so rare when I know of 4 people IRL who have/had persistent symptoms.
One had ED as a young teenager (14 y/o) and I was told that he took Accutane prior.
One was shitting and vomiting blood for 2 years after she took Accutane.
One has treatment resistant depression that began with Accutane.
One said he has had health issues since Accutane but wouldn't state what exactly.
Granted, 3 of these were brought to my attention only because there are people who know of my problems and the ED case was mentioned to me by an ex gf who said that he was the only other person she was ever with who had ED. I only put 2 and 2 together about the ED case after realizing my problems began with Accutane and that there were others like me who took the drug.
Interesting study right here. I know plenty have complained of sinus problems post tane. I've had severe sinus issues myself.
They found p acnes abundant in healthy individuals.
On a side note another study found inflammation that could be caused by retinoids could cause premature thin skin, despite the fact that it increased collagen turnover.
Chronic rhinosinusitis with nasal polyps is characterized by dysbacteriosis of the nasal microbiota
https://www.nature.com/articles/s41598-018-26327-2
This study identifies a difference in nasal microbiota between healthy subjects and phenotypes of CRSwNP patients. Proteobacteria (such asH. influenzae, E.coli, M. catarrhalis) were associated with CRSwNP disease, especially with CRSwNP+A cases, whereas Actinobacteria (such asP. acnes,Corynebacterium spp.) were prevalent in the healthy status.
High-concentration all-trans retinoic acid induces dermal inflammation and reduces the accumulation of type I procollagen in human skin in vivo
[Edited link out]
They are looking at said drugs and some effects on gut microbiota, likemetabolism.
In this study, we demonstrate that these 2 immunomodulatory therapies distinctly alter gut microbial composition in patients with MS.
Inference of functional consequences of alterations in gut microbial composition induced by DMF and GA (MSdrugs)
GA and DMF had a concordant effect on 15 of those pathways, which included pathways affecting vitamin, amino acid, energy, and xenobiotic metabolism. More specifically, among the common concordant pathways affected were retinol (vitamin A), methane, and ethylbenzene metabolism, as well as valine, leucine, and isoleucine degradation
Disease-modifying therapies alter gut microbial composition in MS
MS is believed to result from interactions between underlying genetic predisposition and environmental exposures.1,2Environmental risk factors, including vitamin D levelse1(links.lww.com/NXI/A86), viral exposures,e2smoking,e3and obesity,e4,e5are related to MS onset and disease course. However, most of the environmental risk factors in MS remain unexplained. In consideration of additional potential mediators, the gut is a natural site of investigation, given that it is a major locus of environmental interaction and home to a large portion of the human immune system. In addition, immunologic development and patterning, dysregulated in MS and other autoimmune diseases, is heavily influenced by resident commensal microbes, the microbiota. Gut microbial composition is shaped by both genetics and environmental exposures that begin in utero, providing a potential pathogenic link between these factors and autoimmune diseases such as MS. Studies of experimental allergic encephalomyelitis (EAE) in mice have demonstrated reduced disease severity with administration of oral antibiotics3and established that the presence of commensal flora is required for EAE induction.4
On the possibility of long term retinoic acid accumulation, I havent found anything definitive yet.
But, Ive seen enough recently that maybe there could be a chance. I dont know.
When I think fat tissue, the brain immediately comes to mind.
Retinoic acid is abundantly detected in different depots of adipose tissue by SERS
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5160413/
less is understood about the developmental and metabolic contributions of RA in adipose tissue, partly due to challenge of measuring endogenous RA levels. To our knowledge, only one paper comprehensively quantified endogenous RA levels of different tissues by liquid chromatography coupled with tandem mass spectrometry.13Their results indicate that while liver contains the highest amount of all-trans RA, epididymal adipose tissue is among the second abundant group of mouse tissues together with kidney and brain, when the amount was calculated per weight of tissue.
On Retinoic acid metabolism, this needs to get broke down into 4-oxo-atra before the liver processes it. liver p450 polymorphisms did not make a difference when looking at ATRA metabolism. There's a enzyme outside of the liver that does this. The study wasnt too sure about it yet as of 2015.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352583/
formation of 4-oxo-atRA from 4-OH-atRA appears not to be CYP26A1 mediated in HepG2 cells or in human liver. In HepG2 cells, there was no change in 4-oxo-atRA formation from 4-OH-atRA in the presence of the P450-inhibitor ketoconazole. Surprisingly, the formation of 4-oxo-atRA from 4-OH-atRA was also not decreased in the presence of inhibitors of several alcohol dehydrogenases, aldoketoreductases, or membrane-bound retinol dehydrogenases in HepG2 cells, suggesting that the enzyme responsible for 4-oxo-atRA formation is yet to be identified.
21 hours ago, Calcified said:I think the key point here is sinus problems posttane.
I have had sinus problems for about 2 years now. They started when, which can be found in my previous posts, I trialed a substance called alohol. A odd Russian supplement known for unclogging bile ducts. My theory stemming from discussion of liver flushed over the years was basically a clogged liver was the root cause.
I built up over about 2 weeks of taking larger and larger doses of this stuff expecting at some point to dump a bunch of bile and be cured so to speak. That never happened.
The only side effect was clogged sinus', a strong pressure behind my right eye and sometimes a loss of vision.
I noticed eliminating gluten helped ease the clogged sinus, although I expect this is also related to reducing sugar. Basically now I know anything that will put a strain on my liver will I turn cause my sinus' to block and pressure to come back.
Still on the anti-a diet and will continue indefinitely