Yo mods. I know gladiatoro is an accutane victim as well, but this behavior is just ridiculously idiotic and unhelpful. He's on this forum talking about how he could beat up better and fuck better than anyone here. Does he not realize that this thread is full of people with physical and sexual disability due to this drug? For some people, whatever woopass he could dish out would be a minor nuisance compared to what these victims deal with daily. I don't care if he was born being an idiot like this or if accutane has fried his brain and driven him mad, please take charge against this moron.

Three weeks ago I started my treatment with supplements and a prohormone.
The first week was incredible, I had a high impact on my libido and virility. After the first week, the level has fallen , but still much better than before. Actually, sexual sides are not my main problems. Also I feel high impact on anxiety.
Unfortunately I have not been able to determine any impact on fatigue, pain or vision problems.

I was advised by one good soul from this community to do a protocol with checking up deficiences of copper etc. and buy thiamine and magnesium, and I think it's an approach worth considering, but firstly I want to do a prolonged fasting.

I tried many supplements for these three years and I was sticking with them to this day with no real healing ( but maybe without supplements it would be a lot worse). I eat every day maca powder, spirulina, young barley, crushed eggshells, geese lard- vit.D, gotu kola, recently chondroitin prescribed by my orthopedist, ascorbic acid, shark cartilage. Maybe higher doses of one isolated vitamin or compound would do the trick, but I can't gamble with health anymore.

Fasting is safe and if it won't work, then I will do other protocol.
So I want you to know that I want to do a fast for at least 21 days, I hope you will support me, because it's not an easy task! I want to start tommorow, I won't do any introduction diet, because I already eat quite clean ( maybe except coffee). I will do some kind of colon cleanse though. 

Please be with me and support me a little
Also I would like to read your suggestions if you want to share sth with me.

Kasia 

14 hours ago, Gladiatoro said:

Buying thousands of dollars in supplements for a drug I took 22 years ago thats just plain EVIL .

Giving accutane to kids is fucking child abuse just like vaccines are , evil fucks.

These people are Fucking sociopaths.

You are one crazy man.

I am on Accutane and it is not like child abuse. Accutame does not give permanent side effects to most people. Is it a risk? Yes. Is it a risk worth taking if severe acne is controlling your life? Only an individual can answer. What a rubbish post.

@Kitte
Good luck Kasia. Fasting has helped some in the past and is something that interests me. Here's a study where a fasting mimicking diet was shown to regenerate beta cells in the pancreas: http://www.cell.com/cell/abstract/S0092-8674(17)30130-7 . This could be a potential cure for diabetics, even type one diabetics. Crazy. A suggestion though, maybe start with a 4 day fast first before jumping into a 21 day fast. It would both be safer and maybe as effective. It seems the benefits of a fast come during the re-feeding after the fasting period. During this period there is stem cell generation and HDAC inhibitors like butyrate that hit relevant molar levels and all kinds of promising regenerative things. I know I need to look more into this, but a 21 day fast is a long time without giving your body nutrients.

4 hours ago, Frage said:

@Kitte
Good luck Kasia. Fasting has helped some in the past and is something that interests me. Here's a study where a fasting mimicking diet was shown to regenerate beta cells in the pancreas: http://www.cell.com/cell/abstract/S0092-8674(17)30130-7 . This could be a potential cure for diabetics, even type one diabetics. Crazy. A suggestion though, maybe start with a 4 day fast first before jumping into a 21 day fast. It would both be safer and maybe as effective. It seems the benefits of a fast come during the re-feeding after the fasting period. During this period there is stem cell generation and HDAC inhibitors like butyrate that hit relevant molar levels and all kinds of promising regenerative things. I know I need to look more into this, but a 21 day fast is a long time without giving your body nutrients.

I would suggest smoothies and soup before and after the fast for as long as you possibly can. might
make the fast more effective,

Keep us up-date - we can all support you.

20 hours ago, Gladiatoro said:

Its fucking heart breaking that they are putting kids on this stuff.

These kids have absolutely NO idea what they are getting into down the road.

How many fucking lives have to be destroyed before this drug is pulled off the market.

http://www.nytimes.com/1984/10/29/us/drug-that-often-cures-acne-can-also-cause-birth-defects.html

Is it enough to just say that you shouldn't get pregnant while you are on accutane - I think not!

20 hours ago, Duperele said:

20 hours ago, Gladiatoro said:

Its fucking heart breaking that they are putting kids on this stuff.

These kids have absolutely NO idea what they are getting into down the road.

How many fucking lives have to be destroyed before this drug is pulled off the market.

They don't but their parents should know.

Actually it is the doctors that should know better. They all know what accutane does but because the regulators tell them they can keep on prescribing it they do so without question. Where's the morality in that?
Genocide against young people and so many people are complicit in allowing it to happen - namely DP's, dermatologist, regulators. world health etc, MP's and journalists.
I might add, anyone who doesn't report their sides! Is that to harsh?

Anyone see this:

Mel Gibson and Dr. Neil Riordan talk about mesenchymal stem cells and their success in treating things from physical injuries, to autoimmune diseases, to autism, to even more.
Some of the pfs guys have had Adipose stem cells from their body fat injected into them through IV and miraculously saw significant improvement. Joetz did, Brazilliandude did. What ever happened to this?

edit: I see now, like anything else, adipose stem cell therapy has had varying success for pfs. Still, I feel like almost everyone whos tried it has seen some benefit. And I'm unaware of anyone who has had mesenchymal stem cell therapy. Will have to think about this more.

Another pfs guy, Kentucky, also seems to have recovered to a good level: [Edited link out]
A guy named BP7667 over at propeciahelp only had very slight improvement. The procedure he had though seems alot different from the others mentioned: http://www.propeciahelp.com/forum/viewtopic.php?f=5&t=5387&start=260 (Less volume of stem cells Intravenously)
Theres others who have claimed results over on that site too.

Of course the only thing stopping people from doing this is the cost. Around 20k to do the whole thing in panama. But this is the most promising thing I have seen, by far. If I had 20k I'd do this in a heart beat. And I think I plan to. Is this sane? Obviously I'm convinced. Jesus people these feats seem like miracles

What about people on this thread? I see its been discussed a lot. Even people on pheonixrising have had success with this, to an extent.

Edit: Why is there such little information around about [removed] and this company?
Then theres this stuff that screams scam:

[removed]

Really digging the lions mane.
Very good for my overall feeling well. Probably lifts the depression a bit
Im going to continue this and I also add a new thing

C60. Anybody already used this?
It is known as the most powerful anti-oxidant and rats lived 90% longer on it.

http://c60antiaging.com/c60-faq/how-does-c60-work-as-an-antioxidant/

On 7.2.2018 at 11:32 PM, Gladiatoro said:

Big mouth over the Internet , in person you would surely not talk to me this way as you would get beat up pretty badly , Im 6.4 100 kg of pure muscle from working in construction for 30 years .

Having said that I can post whatever the fuck I want you fucking idiot . And the sex I have is none of your business , trust me my women are always FULLY satisfied , I can have sex for hours on end and you cant due to your trust in allopathic medicine BIG fucking mistake buddy. Its all in the dosage you obviously took too much.

Im probably the LAST guy you want to fuck with .

I went to that site and typed in Aspirin which has over 10000 reported cases of death...

On 2/9/2018 at 4:13 PM, Walden Rev said:

Really digging the lions mane.
Very good for my overall feeling well. Probably lifts the depression a bit
Im going to continue this and I also add a new thing

C60. Anybody already used this?
It is known as the most powerful anti-oxidant and rats lived 90% longer on it.

http://c60antiaging.com/c60-faq/how-does-c60-work-as-an-antioxidant/

Yes, I now take two products by Dr. Stamets' company HostDefense, the Lion's Mane [Edited image out] and [Edited image out]Myco Brain.
I feel especially better taking them as my nerves were a bit "fried" post Accutane.

As for C60, I had no idea it existed. It looks to be cutting edge as far as medical applications. I don't know if I'm brave enough to trial it until there have been some human studies. It looks promising, I will keep an eye out.

But I have some plans for this year for micro dosing psilocybe cubensis and hyperbaric o2 therapy, and possible an HGH (Somatropin) protocol this summer if I can secure the funds. Those are the first three bullets I'm going to use this year to see if I can make any difference in neurogenesis.

A Critical Review on Health Promoting Benefits of Edible Mushrooms through Gut Microbiota

Published online 2017
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618583/

Abstract

The gut microbiota comprises of trillions of bacteria that contribute to the nutrient acquisition and energy regulation [59]. The microorganisms present in the gut play an important role in the health of the digestive system, and also have an influence on the immune system. The immune tissues in the gastrointestinal tract constitute the largest and most complex fraction of the human immune system [60]. We saw earlier that gut microbiota plays an important role in various factors such as physiology, organ development, and aging. We have also discussed the beneficial effects of gut microbiota in various pathological conditions. The medicinal mushrooms can act as immunomodulatory agents to activate gut microbiota. The current review discusses the important areas in mushrooms regulated gut microbiota in the hosts health. We have discussed different mushrooms, their composition, and pharmacological properties, such as antioxidant, hypolipidemic, and atherosclerosis capabilities. We have also discussed some recent research studying the roles of mushrooms in regulating gut microbiota and the mechanism by which mushrooms regulate the gut microbiota.

I think microbiome diversity could be important.

On 2/5/2018 at 4:23 AM, mikez said:

 

Surely, the first step before even considering taking another drug is surely to first check if your own HPA axis is disturbed via blood work similar to that performed in the study?

This study (and most showing HPA dysregulation) are performed while accutane is administered , not after, especially years after.

Our persistent sides can be very annoying, but doing blind tests with potent drugs can also be dangerous.

Completely agree bro. But I and many others are so desperate at this point, I'm more than willing to take risks such as taking a birth control pill. Thing is, its possible (I know unlikely) that HPA disruption by accutane use may have caused an imbalance in receptor expression which persisted after the HPA axis normalised. As such its possible hormonal tests show normal hormones as most post-accutane hormone tests show, despite an issue with receptors. I'm still waiting on cortisol, progesterone tests. But my DHEA-S were very high, out of the scale. This is a HPA hormone.

I know a PAS guy who is trying RU. I intend to try myself. I will let you know how it goes.

Most important thing right now is, gather info, resources and MONEY. If there is any chance of getting any justice in regards to lawsuits or development of a treatment. We will need money. It will be PAS people who will need to fund this stuff. I know that is very unfair and not right, but it seems like the most likely outcome.

People can moan about the corruption of big pharma all they want. Aspects of pharma are "evil" as are many aspects of most industries. But no amount of shouting about the evils of pharma or roche online is going to change anything. We need to develop possible theories of how our symptoms may have occurred cited with references. We need to test these theories with evidence and/or protocols. Eventually we need to fund our own study/studies and potentially even fund a law suit. But for any of this, we need info and MONEY. Nobody else is going to fund these studies for us.

I always wonder how much more we could know about these conditions if we had a few million dollars to invest in studies. Simply investigating the hormones/neurosteroid levels and brain scans measuring dopaminergic activity in response to sexual stimuli or dopamine agonists compare to controls, could tell us so much about how these side effects have persisted and potential treatment options.

Bottom line is, nobody from roche or any pharma company is going to fund or bother researching this stuff. Right now, the most effective thing any of us can do is. Research online, save money to donate towards a future study or go to university and study medicine/biology/neuroscience. We need a few phd research groups to get interested in this stuff.

We have to think realistically and long term.

Accutane is derived from vitamin a. Overdosing on vitamin a, will produce the same effects of accutane, but, with more side effects, it may not last as long as accutane does as well. Accutane is a retinoid (which there are retinoid receptors in your cells), accutane is 13-cis-retinoic acid, or isotretioin. Your liver makes a little bit of isotretioin on its own. Though accutane is synthetically made. I am not a chemist, so I do not know all the differences between the two. Overdosing on vitamin a, will give you dry skin, etc. And doctors used high doses of vitamin a for acne in the 1920's, until they found out it was toxic so the stopped immediately. Taking 15,000 IU's of retinol a day, and if you are healthy, will not kill you. Taking hundreds of thousands a day (which that is how much is needed to produce the same effects as accutane has on you) will eventually cause many problems. Vitamin a is fat soluble, so it will add up eventually. There is a lot of hype about vitamin a being the evil one on these boards. That isn't true.

I remember when I did my Accutane treatment in 2011 I was told to not overdose by taking vitamin A, among all things we are instructed to avoid, such as intense activities, exposing the skin to the Sun, etc.

https://www.anabolicmen.com/vitamin-a-testosterone/

I wonder if vitamin A also explains the side effect of low libido and lower testosterone levels
https://rxisk.org/accutane-30-years-of-trading-our-sex-lives-for-clear-skin/

What I can tell is that perhaps the diet I adopted in the last 5-10 years might have contributed to that, since I included (for example) skimmed milk andricotta cheese in the breakfast... both are not rich in fat and this is detrimental if the goal is to have more testosterone:
https://www.anabolicmen.com/fats-and-testosterone/

I decided that I'll visit a second nutritionist (it's always good to get a second opinion), in my view more qualified than the first, after April. In the meantime I am getting rid of the plastics (BPA) and replacing all my personal care products (toothpaste, soap (bar/liquid), shampoo, foot moisturizer, sunscreen protector,deodorant...) for non-toxic versions to see if things will improve, since there's always some scientific study saying that fluoride, phthalates and other stuff can contribute to lowering testosterone.

Important: It's a waste of time trying to argue with most doctors, they will only look at numbers and tell we are not sick, even though the figures are low, as predicted by that Rxisk article:

A battle of wills

Visits to the doctor can become a battle of wills when a generally healthy looking young person walks through the door complaining of erectile dysfunction or other sexual symptoms. Many of us face difficulty when we try to implicate a drug we are no longer taking as the cause of our continued sexual dysfunction.

In the event that a conventional test for hypogonadism is conducted, results typically fall within the normal reference range. Male sufferers of our condition will often be told by endocrinologists that their testosterone is a little low for their age but is not low enough to warrant treatment.

Even for those who have discovered hormonal imbalances after seeking medical attention, hormone replacement therapy (HRT) has done little to provide adequate symptom relief, even under the care of doctors whose specialty is HRT.

The fact that someone with prolactin levels of 100 or higher can benefit from a drug like Cabergoline more than I (and in my case perhaps this kind of drug is totally unnecessary) doesn't mean I don't have any health problem. That is the case because PRL levels for a man should always stay below 10. More than that means low libido and ED. My levels were 25-25-28 and recently 20.

The fact that men with total testosterone levels below 300 ng/dL havehypogonadism/needtestosterone replacement therapy (an artificial way to increase it, also with side effects and possibly for a long time, if not for the rest of life, just like Cabergoline) and I was able to increase my 309 result (26 for vitamin D) to 419 after 3 months taking 2000 IU/day of vitamin D-3 doesn't mean I am OK.

419 is still very low, and it's not far from below 300, a 35% increase due to vitamin D is nothing, if we were talking about 100% and a total testosterone of 600 (plus a PRL no higher than 10) I would agree this is an improvement and I am back to my old self.These doctors are useless and only read things without questioning or thinking what should be the real measure of health.

With all these vitamins and changes in my lifestyle I doubt things won't improve. But it's obvious I will have to improve my health more than ever before, just to fight this side effect from Accutane. The lack of blood test results from all individuals affected with low libido and ED after taking Accutane unfortunately contributes a lot for many people to argue this can only be solved by psychiatrists, even though it has been established that depression was ruled out as a factor to cause these issues.

I might have felt depressed 2-3 years after the treatment, yet now the depression is gone. It couldn't stay for the rest of life.

There are no blood test results from the affected and we have no idea what kind of life they have, what they eat or use on a daily basis. All these things need to be investigated, just like that scientific study from 2007 (later refuted) that said the following:
http://www.peaktestosterone.com/forum/index.php?topic=2273.msg21179

I mentioned before (vitamins D/E, omega 3 fish oil, probiotics, vitamin B-6, which I'll investigate if it's safe to take at least no more than 20-25 mg/day, Whey Protein/Creating (which will both help with the goal of increasing testosterone by changing the workout routine *)

* http://www.mercola.com/testosterone.aspx (see High-intensity interval training / Strength training)

One thingthing I'll question the 2nd nutritionist is if increasing the protein intake for gaining lean mass and being able to do all these intense exercises is not going to thwart the very goal of increasing testosterone, I always read that a diet should have 40-60% of carbohydrates and no more than 30% proteins and 30% fat. The 1st nutritionist prescribed one with more protein than the rest. My guess is that for the first months the protein intake needs to increase and in the future we need to balance the diet, with more fat and carbohydrates. All these questions will be asked in my next visit. Remember them.

Hello members,
It seems some have taken exception to others posting in this forum recently. You may find that some people post a number of similar posts and you may think sometimes these are irrelevant to your interpretation of the thread you are commenting in but please remember that this is a PUBLIC forum and remind yourself of the community rules. Posters come and go and move on to other topics but if you make aggressive, mean spirited posts in poor taste to discourage them that just incites similar responses and you may find yourself the recipient of warning points and censorship. Remember that you can start a new thread on your particular interest.
There may be a feature coming to the site that will allow you to block seeing other members posts if you find there is someone whose thoughts you're not interested in. Introduction of this feature is outside of the scope of moderators so patience please.
Anyway, carry on and try your best to be civilised and mature in your posting.
Do report behaviour you consider inappropriate but accept that moderators, although sympathetic to your concerns, may not always agree with your suggested action based on the community rules.

48 minutes ago, Perene said:

Accutane is derived from vitamin a. Overdosing on vitamin a, will produce the same effects of accutane, but, with more side effects, it may not last as long as accutane does as well.

I posted this not too long ago.

comparing Accutane (13-cis) to retinol
Just looking at weight, 40mg Accutane equals 133,000iu vitamin A.
This cant be too far off, their structures look very similar.
https://en.wikipedia.org/wiki/Retinoid

So you figure this number 133,000iu everyday for 3 to 4 months (average length of treatment)
13-cis is a analog of vitamin a. It reminds me of some of the things i've been looking at with k2. mk7 being an analog of vitamin k.
Do we know the benefit of isotretinoin over retinol? Or why it was preferred over retinol?
Obviously you can't market and sell something with nearly as much profit that's already available as a nutritional supplement.
That's one reason.
I thought another reason was isotretinoin did not accumulate like retinol did?
I would think in their testing it would have been easy enough to kill some rats, dissect the livers, and measurevitamin a content.
It also would have been a concern I could imaginethat they had some knowledge of (liver toxicity from hypervitaminosis A ) at the time.

You see its not just Accutane.

Study Links Excess Vitamin A and Birth Defects - NYTimes.com

On 2/10/2018 at 2:34 AM, macleod said:

Yes, I now take two products by Dr. Stamets' company HostDefense, the Lion's Mane [Edited image out]and [Edited image out]Myco Brain.
I feel especially better taking them as my nerves were a bit "fried" post Accutane.

As for C60, I had no idea it existed. It looks to be cutting edge as far as medical applications. I don't know if I'm brave enough to trial it until there have been some human studies. It looks promising, I will keep an eye out.

But I have some plans for this year for micro dosing psilocybe cubensis and hyperbaric o2 therapy, and possible an HGH (Somatropin) protocol this summer if I can secure the funds. Those are the first three bullets I'm going to use this year to see if I can make any difference in neurogenesis.

Host defenses products are a bit controversial on Reddit.
The general consensus is that the brand Real Mushroom is top notch

https://www.amazon.com/Mushroom-Extract-Powder-Real-Mushrooms/dp/B01DKZZFCE

I do urge to try different brands of Lions mane, some gave me sleepiness and some gave me alot of energy. Right now I mix some.

I personally use 2 versions right now and benefits are most prominent after 4/5 months.
But the short term right now I have amazing mood/wellbeing. So fucking nice again.

https://www.ebay.co.uk/itm/Lions-Mane-Mushroom-10-1-Dual-Extract-40-Polysaccharides-x90-Capsules-Organic/112613304042?epid=4003874346&hash=item1a3846a6ea:g:rXkAAOSwSrNZ7MQe#rwid

https://www.vitaminesperpost.nl/hericium-erinaceus-extract?gclid=Cj0KCQiAzfrTBRC_ARIsAJ5ps0sC_95K2bLMo4wkUgZcMhQHTUvmnI_om9Gnq60_LAqm-UAdMg257LsaAkItEALw_wcB#product_tabs_samenstelling

As for the C60, it cleans up the body at DNA level, so I put my money on this one. I honestly think after RSO this will benefit me the most.
Most people report alot of improvement in the fatigue area and alot of imporvement in the exercise area which have greatly diminished after tane.

• Body temperature went from 96.6(+/-.5) to mid 97's (verified by 2 different probes, with 5 samples at 9am, 1pm, 3:3pm, 5pm and 8pm)
• My energy levels have dramatically increased. It feels 'normal' for me now.
• I am actually experiencing some insomnia. (Good thing?)
• My 'lay in bed and think of stuff' before sleeping for most of my life was absent for nearly 9 months. It has kind of returned.
• I seem to 'smell' better now. Not annoying, but when you eat your favorite food and you can smell it as it used to be (stupid allergies)
• I seem 'happier' - GABA upregulation?
• More calm. Less stressed.
• My frequency of urination has increased, to nearly pre-Levaquin levels.
• Mental clarity has increased by at least 2 orders of magnitude. People have been telling me I'm much more like my old talkative self.
• Less anxiety overall.
• Vivid, Awesome dreams. I can't explain it, but I had a dream I was on vacation and having fun, doing all kinds of stuff. It was so vivid. Never had that before. To be fair, might be placebo.

Update for 7/21/16:

• Someof the effects are kind of wearing off - This might be a dosage issue. I was taking 3mg to 5mg a day, I think I should have reduced it to maybe 1mg a day. Some users report that it does nothing for them, but for me, it did a lot which shows me that something is wrong with my antioxidant systems within my body (or I have mitochondrial dysfunction)
• I still have some pretty good dreams.
• My blood is bright red and my o2 stats on a pulseox are between 100 and 102 - I suppose oxygen saturation has increased?
• Respiration rate has reduced from 18 to 12 when sitting.
• Pulse rate is unchanged
• My hair growth rate seems to have increased. (Might be placebo - but other users on another forum are reporting it as well)
• I had thinning hair on the very top of my head - It seems to be coming in (might be placebo - But again, other users are reporting it)
• Skin texture on my face seems 'different' - not as pronounced with age/sun damage (other users are reporting skin texture changes)
• Eye floaters, which increased post-Levaquin, have decreased quite substantially
• Memory is not back to normal (from a year ago, as an example) - But so much better. This is definitely not placebo.
• Energy levels are steady, but not at their peak, and still much better overall. My insomnia has faded. I actually slept 10 hours the other day, probably because I hardly slept for 3 days.
• Body temperature is between 96 and 97 - But mostly in the upper 96 range.
• Mood is still pretty good overall.
• I do not get sore after physical activities as much as I used to.
• My creativity has increased and my production is at least 40% better than a month ago.

18 hours ago, flynn said:

Completely agree bro. But I and many others are so desperate at this point, I'm more than willing to take risks such as taking a birth control pill. Thing is, its possible (I know unlikely) that HPA disruption by accutane use may have caused an imbalance in receptor expression which persisted after the HPA axis normalised. As such its possible hormonal tests show normal hormones as most post-accutane hormone tests show, despite an issue with receptors. I'm still waiting on cortisol, progesterone tests. But my DHEA-S were very high, out of the scale. This is a HPA hormone.

I know a PAS guy who is trying RU. I intend to try myself. I will let you know how it goes.

Most important thing right now is, gather info, resources and MONEY. If there is any chance of getting any justice in regards to lawsuits or development of a treatment. We will need money. It will be PAS people who will need to fund this stuff. I know that is very unfair and not right, but it seems like the most likely outcome.

People can moan about the corruption of big pharma all they want. Aspects of pharma are "evil" as are many aspects of most industries. But no amount of shouting about the evils of pharma or roche online is going to change anything. We need to develop possible theories of how our symptoms may have occurred cited with references. We need to test these theories with evidence and/or protocols. Eventually we need to fund our own study/studies and potentially even fund a law suit. But for any of this, we need info and MONEY. Nobody else is going to fund these studies for us.

I always wonder how much more we could know about these conditions if we had a few million dollars to invest in studies. Simply investigating the hormones/neurosteroid levels and brain scans measuring dopaminergic activity in response to sexual stimuli or dopamine agonists compare to controls, could tell us so much about how these side effects have persisted and potential treatment options.

Bottom line is, nobody from roche or any pharma company is going to fund or bother researching this stuff. Right now, the most effective thing any of us can do is. Research online, save money to donate towards a future study or go to university and study medicine/biology/neuroscience. We need a few phd research groups to get interested in this stuff.

We have to think realistically and long term.

Just out of interest - where are you from and have you reported your side effects?

https://www.theguardian.com/society/2004/oct/20/health.medicineandhealth

What will it take to get you all to report your side effects?

In the procedure that resulted in labelling erectile dysfunction and reduced libido, all sexual side effects were analysed. As outlined in the CMD(h) report previously sent to you, and attached here, the number and strength of cases of erectile dysfunction and reduced libido were sufficient to warrant regulatory updates to the product information. For other sexual side effects in the regulatory classification category of Sexual function and fertility disorders there was judged to be insufficient evidence to justify updating the product information. There are no data to determine the duration of these side effects but a positive dechallenge (patient recovered when the drug is stopped) was reported in 15 cases included in the review. In the other cases there was either no report of duration of symptoms or no information at all provided on duration.

The effect of isotretinoin on human male fertility has been studied. The current information in the isotretinoin SmPC on male fertility states that, Isotretinoin, in therapeutic dosages, does not affect the number, motility and morphology of sperm and does not jeopardise the formation and development of the embryo on the part of the men taking isotretinoin.

Having read the above it seems that the sexual sides are lot lasting - how brilliant is that?
So you should all be better soon!

If you do believe you have lasting sexual sides then bloody report it.

If anyone wants guidance of how to report please PM me.
If anyone wants to give me their experience PM and/or I will give you my email address.

3 hours ago, hatetane said:

Just out of interest - where are you from and have you reported your side effects?

https://www.theguardian.com/society/2004/oct/20/health.medicineandhealth

What will it take to get you all to report your side effects?

In the procedure that resulted in labelling erectile dysfunction and reduced libido, all sexual side effects were analysed. As outlined in the CMD(h) report previously sent to you, and attached here, the number and strength of cases of erectile dysfunction and reduced libido were sufficient to warrant regulatory updates to the product information. For other sexual side effects in the regulatory classification category of Sexual function and fertility disorders there was judged to be insufficient evidence to justify updating the product information. There are no data to determine the duration of these side effects but a positive dechallenge (patient recovered when the drug is stopped) was reported in 15 cases included in the review. In the other cases there was either no report of duration of symptoms or no information at all provided on duration.

The effect of isotretinoin on human male fertility has been studied. The current information in the isotretinoin SmPC on male fertility states that, Isotretinoin, in therapeutic dosages, does not affect the number, motility and morphology of sperm and does not jeopardise the formation and development of the embryo on the part of the men taking isotretinoin.

Having read the above it seems that the sexual sides are lot lasting - how brilliant is that?
So you should all be better soon!

If you do believe you have lasting sexual sides then bloody report it.

If anyone wants guidance of how to report please PM me.
If anyone wants to give me their experience PM and/or I will give you my email address.

I'm from the UK. I have already reported it.

The problem here is how people are measuring sexual sides. Sexual sides don't necessarily mean altered sperm and testicular function or erectile function.

Sexual sides can also mean loss of libido, interest in sex, loss of nocturnal and morning erections etc. The problem here is that its very difficult to test these things in a model such as a rat. Also given the embarrassing nature of these side effects, I would be they are significantly under-reported. Either because

1. People don't want to report them
2. People haven't made the connection between their sexual side effects as accutane (note it's taken me 10 years to make the connection).
3. People who have these side effects are almost in denial about them and try as hard as they can to ignore that they even exist.

I agree these side effects needs to reported far more frequently.

On 2/9/2018 at 7:37 AM, draci said:

I went to that site and typed in Aspirin which has over 10000 reported cases of death...

Try filtering results by age groups expected to take Isotretinoin, then consider how many people used Aspirin compared to Accutane. Only ~2,700 deaths for Aspirin in the 12-64 age group, which I admit is a poor age range (includes people in their 40s - 60s) to compare to the age range of people typically prescribed Accutane.

Also turns out daily Aspirin might not be as harmless as once thought:
http://www.newsweek.com/aspirin-every-day-increases-risk-serious-bleeding-625364

Either way, neither of us could make a strong argument with the data presented.

Point wasn't to be alarmist, but to show that the FAERS system is actually a pretty good tool for perusing side effects. Would be nice if they would give the estimated total use of the drugs listed and allow comparisons with rates of certain side effects compared to all other drugs.

18 hours ago, guitarman01 said:

I posted this not too long ago.

comparing Accutane (13-cis) to retinol
Just looking at weight, 40mg Accutane equals 133,000iu vitamin A.
This cant be too far off, their structures look very similar.
https://en.wikipedia.org/wiki/Retinoid

So you figure this number 133,000iu everyday for 3 to 4 months (average length of treatment)
13-cis is a analog of vitamin a. It reminds me of some of the things i've been looking at with k2. mk7 being an analog of vitamin k.
Do we know the benefit of isotretinoin over retinol? Or why it was preferred over retinol?
Obviously you can't market and sell something with nearly as much profit that's already available as a nutritional supplement.
That's one reason.
I thought another reason was isotretinoin did not accumulate like retinol did?
I would think in their testing it would have been easy enough to kill some rats, dissect the livers, and measurevitamin a content.
It also would have been a concern I could imaginethat they had some knowledge of (liver toxicity from hypervitaminosis A ) at the time.

You see its not just Accutane.

Study Links Excess Vitamin A and Birth Defects - NYTimes.com

www.nytimes.com/1995/10/07/.../study-links-excess-vitamin-a-and-birth-defects.html

Oct 7, 1995 -Women who consume excessive amounts ofvitaminA during the early months of pregnancy can cause seriousbirth defectsin their unborn children, a large new study has shown. ... The study showed that 1 baby in 57 born to women taking doses ofvitaminA above 10,000 international units daily was damaged as a result.

There is a study showing measured conversion rates of Isotretinoin to 4-oxo-Isotretinoin, All-trans retinoic acid, 9-cis retinoic acid, and some other metabolites. So there's not a true 1:1 conversion of 13-cis to All-trans retinoic acid, but almost certainly still what would be considered a toxic level of All-trans while on the drug, ( going by the retinol equivalent of a toxic dose.)

Another study showed there was a small percentage of individuals who had a very high (think it was around 5x greater than mean average)
level of all-trans retinoic acid detected in their blood after taking the same dose of isotretinoin as the rest of the group.
Maybe most of us who were severely affected were among that small percentage?

Can't seem to find either study though. I'll post them for you if I come across them.

.

3 hours ago, Dubya_B said:

Another study showed there was a small percentage of individuals who had a very high (think it was around 5x greater than mean average) level of all-trans retinoic acid detected in their blood after taking the same dose of isotretinoin as the rest of the group.

That is the single most interesting piece of information I have read regarding this Accutane mess in the past few months! This is the type of science-based discussion we need. Differences in how individuals metabolize drugs has been acknowledged for other drugs (e.g., antidepressants) in the past. However, I have yet to see that discussed for Accutane. From what I understand, All-trans retinoic acid is the "chemo" aspect of Accutane; it's what drives the apoptotic effects of the drug, which as many of us know have been observed in multiple organ systems. If a subset of Accutane users are processing the drug differently and consequently getting an especially hefty dose of this lethal metabolite, that may be an important part of the puzzle. Let me know if you find the study.

That being said, I have been thinking about the study you shared which listed the gene changes associated with the drug. I remember you mentioning you had access to a program that allows you to input a gene to learn about its association with various health markers. Do you mind sharing that again? I would like to investigate that myself.

@ACCUiTy_drANE Thanks.

I'll be damned for not bookmarking that study I mentioned. It discussed highly variable levels of metabolites after some duration days or weeks into treatment.

On a related note, here is an interesting bit from the Australian product leaflet for Isotretinoin:
http://www.medicines.org.au/files/chpisotr.pdf

Quote

Pharmacokinetics
Absorption
There is considerable inter-individual variation in the bioavailability of oral isotretinoin. After oral administration of 80 mg isotretinoin (2 x 40mg capsules) given in the fasting state, peak plasma concentrations ranged from 167 to 459 nanogram/mL and mean time to peak was 3.2 hours in healthy volunteers, while in acne patients peak concentrations ranged from 98 to 535 nanogram/mL (mean 262 nanogram/mL) with a mean time to peak of 2.9 hours. The bioavailability of isotretinoin capsules taken with food is 1 to 2 times greater than when taken in a fasting state.

Might be more of a matter of highly-varying absorption in different people than varying metabolism. It could also be that retinoids are just plain very difficult to test accurately in blood.

Another insanely-wide range of bioavailability:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360017/figure/fig3/

If you look at the whole of the above study, you'll see the standard deviation of the data complementary to that table was almost as great as the mean!

Here is the post with links and instructions for a couple gene-set analysis tools:

Quote

Here is a list of genes with >2.0 fold-change from a study called "Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action":

MSMB COL1A1 HAO2 HSD3B1 THEDC1 SLCO4C1 MLSTD1 PLA2G7 FADS1 GLDC GAL PDZK1 FABP7 HIST1H1C FABP7 ALOX15B MUC1 INSIG1 HMGCS1 BG1 SOAT1 FADS2 CRAT MAC30 ZAP128 CHI3L1 APOC1 HSD11B1 TMPRSS11E PECR SAH HGD DHRS9 SRD5A1 CIDEA SEC14L4 ME1 PDE6A NSDHL ACAT2 FA2H FDPS GK HMGCR

1. Go to DAVID Functional Annotation Tool: [Edited link out]
2. Select "Upload" on the left-hand side of screen.
3. Copy/paste the above list into input box and select "Official_Gene_Symbol" from "Select Identifier" drop-down list. Tick "Gene List" radio button as "List Type"
4. You will be prompted to select species. Choose "Homo sapiens" from combo box
5. Select "Background" on the left-hand side of screen.
6. Choose "Homo sapiens" from list and click "Use"
7. Click "Start Analysis" on navigation bar or select "Functional Annotation Clustering" buttons

You should see different biological pathways associated with the differentially expressed genes. If you set it to the highest stringency, you can see the cholesterol, sterol, and steroid biosynthetic pathways are strongly associated with the list of genes.

I like the reports generated by KOBAS 3.0 better: [Edited link out]
...but you have to convert the list of gene ID names to Entrez or Ensemble IDs using a tool like this: [edited link out]

I ran the converted list of Ensemble IDs through KOBAS and only used the disease databases. This showed the FADS1 and FADS2 genes, that were both decreased ~3.5 fold in the "Temporal Changes" study, are associated with Crohn's, Ulcerative Colitis, and Inflammatory Bowel Disease. Looking at the literature, decreases in metabolism of these enzymes and decreases in their transcription are strongly associated with IBD sand Crohn's, both supposed side-effects of Accutane/Isotretinoin. The MUC1 (mucin) gene, that promotes maintenance of the mucus-lining of intestinal tract was also associated with these diseases and decreased many-fold in the "Temporal Changes" study.

Something to keep in mind is that all of these different functional annotation tools will give somewhat different results. The results I got for the gene-set listed above using DAVID pretty well matched the results discussed in the study, where the author used an older version of DAVID.

EDIT: Just tried DAVID and KOBAS, and neither seems to be working properly now.

For a trial run with something on a site that actually works:

Go to Gene Ontology Consortium's Panther tool here: http://pantherdb.org/index.jsp

1) Copy gene list in above quote and paste it into text box in Panther tool

2) Select list type: "ID List" with radio button

3) Select organism: "Homo sapiens"

4) Select Analysis: For simplicity on the first run choose "functional classification viewed in pie chart" radio button

5) Click "Submit"

You can click through the different pie chart views for more details, and/or go back to the main page and try the different radio buttons under "Select Analysis" for more info. ...These types of tools are always frustrating to use until you get the hang of them.

Hard to explain this stuff in detail, I don't completely understand how it works,, but it basically makes associations among the gene set and databases with listings of their biological characteristics (structure, function, cellular location, associated disease states, interactions amongst each other at the protein/RNA level, etc...).

There are even better tools available now for gene-set analysis that weigh the values for observed fold-change into the analysis.

You might also like the tool Mario Vitali recommended for making disease associations: [Edited link out]

On 2018-02-07 at 10:38 PM, Gladiatoro said:

A guy I know took a flu shot got kidney failure now he is in a fucking wheel chair. Lies lies and more lies.

And one guy said he cant get an erecting under any circumstances even with viagra after tan exposure , thats fucking pathetic he is only 30.

My skin looks great but never having sex again is fucking heart breaking.

Well sex is really not only about getting an erection, you can have perfectly fine sex without using your penis.

2 hours ago, Duperele said:

On 2/7/2018 at 4:38 PM, Gladiatoro said:

A guy I know took a flu shot got kidney failure now he is in a fucking wheel chair. Lies lies and more lies.

And one guy said he cant get an erecting under any circumstances even with viagra after tan exposure , thats fucking pathetic he is only 30.

My skin looks great but never having sex again is fucking heart breaking.

Well sex is really not only about getting an erection, you can have perfectly fine sex without using your penis.

That's new.... I'm not familiar with how sex works for guys on other planets though.

Pleasuring someone else without being able to feel sensations of pleasure yourself isn't my idea of "perfectly fine". Most women I know aren't fond of the idea of a non-mutual arrangement either.

Thanks Accutane!

.

Hey guys I want to give you an update on my situation. I got bad news..
My recovery was 100% real and I was feeling absolutely awesome for the last couple of months but I have to say the last weeks and espaciallly the last couple of days I feel that I am loosing my sexdrive slowly. Not that bad so far and I'm still 10 times better than before the use of fin but honestly at the moment I can't say that I am still fully recovered. One interesting fact is that my situation was getting worse again when I took cocaine about 1 month ago and I couldnt have sex because my dick wasn't working.
So I it scarred me a little bit and since that moment it goes down the road.