8 hours ago, TrueJustice said:

Is that why we sometimes feel better during and after alcohol or is that more to do with releasing endorphins?

Also, can someone please state which specialty these artery issues relate too?

Is it a heart specialist we should see?

Alcohol has anti inflammatory effects. Too much can have a negative effect on vascular constriction.

[Effect of alcohol on vascular function]. - NCBI

Im looking into some tests. The least you could do is ekg if you've never had one at your age, your primary might even be able to do this. Make sure you see the report.
"CAROTID INTIMA MEDIA THICKNESS TEST " like in the studies.
I thought I was getting this test through http://www.lifelinescreening.com/ , turns out their ultrasound doesn't look at this. There is a more accredited place though im going to check.

We're on page 608 and were talking about drinking gin.
good idea let's all do that for experimental purposes

@Frage @guitarman01

Guitarman, implying that excess 13-cis or all-trans retinoic acids could somehow block or mitigate beneficial effects of retinol on maintaining stem cells?

Makes sense. Something interesting is that the few studies of epigenetic effects of Accutane or all-trans retinoic acid indicate a general trend toward genome-wide demethylation more so than methylation.

All of those with PAS, or even those with PFS, who are aiming to promote demethylation could be going in the completely wrong direction. There is a good chance some genes got "switched on" that shouldn't have been and this is at the core of the various symptoms associated with either syndrome, but we have some evidence this may true of post-Accutane at least.
For instance, Melnik discusses an increase of inducers of p53 (protein that promotes apoptosis) as a possible mechanism of adverse reactions.

Frightening stuff about Accutane causing arterial thickening. That study focused on the corotid artery because it is rather easy to observe with ultrasound. This effect is also though to be system-wide. It is stated in the study that ultrasound of the corotid artery showing thickening of the walls "is now recognized as an indicator of atherosclerosis."

Guys help please. I am trying to collect data to produce a document to view.

I have MHRA stats but i need world info and more realistic accounts.

For instance the propecia foundation state that nearly 3000 men have reported erectile dysfunction as compared to UK approx. 300

I have asked WHO to provide this info but I may not receive it the time frame I have.
So accurate data and good scientific papers especially those related to sexual sides would be really useful.

Less than 50 men have reported ED to MHRA and we all know these figures do not present the true numbers,

All info needs a reference.

Thanks

https://www.acne.org/messageboard/profile/129604-abcabc/?tab=forums_topic_post

Fasting apparently helped this guy for anyone who hasn't already seen it.

7 hours ago, Dubya_B said:

Guitarman, implying that excess 13-cis or all-trans retinoic acids could somehow block or mitigate beneficial effects of retinol on maintaining stem cells?

Makes sense. Something interesting is that the few studies of epigenetic effects of Accutane or all-trans retinoic acid indicate a general trend toward genome-wide demethylation more so than methylation.

All of those with PAS, or even those with PFS, who are aiming to promote demethylation could be going in the completely wrong direction. There is a good chance some genes got "switched on" that shouldn't have been and this is at the core of the various symptoms associated with either syndrome, but we have some evidence this may true of post-Accutane at least.
For instance, Melnik discusses an increase of inducers of p53 (protein that promotes apoptosis) as a possible mechanism of adverse reactions.

Frightening stuff about Accutane causing arterial thickening. That study focused on the corotid artery because it is rather easy to observe with ultrasound. This effect is also though to be system-wide. It is stated in the study that ultrasound of the corotid artery showing thickening of the walls "is now recognized as an indicator of atherosclerosis."

I guess I'll just go down the line here with my main takeaways. I try to always look for key takeaways to keep things simple and leave as little room as possible for overinterpretation, the problem is normally with the conflicting studies themselves.

For example true or untrue?

All-trans retinoic acid induces nerve regeneration and increases serum and nerve contents of neural growth factor in experimental diabetic neuropathy.

The first couple studies I was actually looking for possible anti aging properties of Accutane.
I didn't realize initially the first study was exclusive to retinol but then I found a very similar study for retinoic acid.
The retinol exclusive actions are interesting, but then this plays into the whole idea that there is still a conflict with 13-Cis many years later in the body.
Meaning you would think this would revert back to normal if Accutane is long gone.
I have also had no luck supplementing vitamin a on numerous occasions and only made things worse I think in the long run. I can look at the extra wrinkles in my hands or my eye floaters as examples.
Funny how you hear some people say post disorders, if I never took this or that... It made me so much worse and I never recovered. What is happening here?

Looking at methylation it doesn't seem like its gotten people very far. I've looked at it, its been looked at for years on here as well. One thing I will say, looking at any supposed liver toxicity, (maybe you could include inflammation as well) there are studies out there that show liver toxicity induced hypermethylation that lead to cell death. Im sure you could find conflicting studies though like you mentioned.
There's one study I found, id like to try to find it again. I think it was some form of vitamin a toxicity, I forget which metabolite. Basically the gist was too much vitamin a induced cellular chaos or dysregulation in the liver. Vitamin K restored this chaos back to a normal state. The verbiage was much more technical than that of course.

Some of the ideas out there are kind out there. some generated from pfs forums.
Accutane people take Fin
Fin people take SSRI's
SSRI people take low dose SSRI.

The last one though on the artery thickening is my biggest concern atm. Gradual vascular remodeling.
The body will compensate for this, but its not the same.
This might be where your premature aging comes from. It would involve bone structure as well.
Actually my biggest concern is how long some subtle problems might have been going on already for some people.
Maybe since birth, and drugs like Accutane just kicked things into high gear and made it a big problem.

Right here. Simple possible connections. Even if you don't always read me type it, I want to emphasize this, Im always thinking this.
What might be possible.
Because we have all been wrong to a certain extent up to this point.

Dyslipidemia and Risk of Coronary Heart Disease: Role of Lifestyle ...

Vitamin K is known to regulate cellular processes other than -carboxylation, such as electron transport, anti-oxidation and lipid biosynthesis, which could potentially be inhibited by ____________

I continue to look at this because it continues to show a trail.
Whats the biggest problem in all of this? Your trying to correct something that has been going on for decades in some of you. Therecomes a certain point in time where you can only turn back the clock so far, even if the absolute cause was found. Not saying its this. Yet. But there are a few more things to explore that I can show you.

Vitamin K deficiency reduces testosterone production in the testis through down-regulation of the Cyp11a a cholesterol side chain cleavage enzyme in rats

https://www.sciencedirect.com/science/article/pii/S0304416506001590

It is known that K is not only distributed in the liver and bones but also abundantly distributed in the brain, kidney, and gonadal tissues. However, the role of K in these tissues is not well clarified. In this study, we used DNA microarray and identified the genes whose expression was affected in the testis under the K-deficient (K-def) state. The expression of genes involved in the biosynthesis of cholesterol and steroid hormones was decreased in the K-def group. The mRNA levels of Cyp11a a rate-limiting enzyme in testosterone synthesis positively correlated with the menaquinone-4 (MK-4) concentration in the testis. Moreover, as compared to the control (Cont) and K-supplemented (K-sup) groups, the K-def group had decreased testosterone concentrations in the plasma and testis. These results suggested that K is involved in steroid production in the testis through the regulation of Cyp11a.

3 hours ago, guitarman01 said:

I continue to look at this because it continues to show a trail.
Whats the biggest problem in all of this? Your trying to correct something that has been going on for decades in some of you. Therecomes a certain point in time where you can only turn back the clock so far, even if the absolute cause was found. Not saying its this. Yet. But there are a few more things to explore that I can show you.

Vitamin K deficiency reduces testosterone production in the testis through down-regulation of the Cyp11a a cholesterol side chain cleavage enzyme in rats

https://www.sciencedirect.com/science/article/pii/S0304416506001590

It is known that K is not only distributed in the liver and bones but also abundantly distributed in the brain, kidney, and gonadal tissues. However, the role of K in these tissues is not well clarified. In this study, we used DNA microarray and identified the genes whose expression was affected in the testis under the K-deficient (K-def) state. The expression of genes involved in the biosynthesis of cholesterol and steroid hormones was decreased in the K-def group. The mRNA levels of Cyp11a a rate-limiting enzyme in testosterone synthesis positively correlated with the menaquinone-4 (MK-4) concentration in the testis. Moreover, as compared to the control (Cont) and K-supplemented (K-sup) groups, the K-def group had decreased testosterone concentrations in the plasma and testis. These results suggested that K is involved in steroid production in the testis through the regulation of Cyp11a.

What have you done to test this theory...?

Looking at what I just posted, if someone had low testosterone for their age, you would literally be looking to see if k2 mk7 at the right dosage and duration was capable of raising testosterone levels. You could also look atestradiol as well. You would be looking at "before" and "after" blood tests.

Vitamin K2 directly inhibits new estrogen synthesis

https://www.ncbi.nlm.nih.gov/pubmed/15763078

8 hours ago, guitarman01 said:

Looking at what I just posted, if someone had low testosterone for their age, you would literally be looking to see if k2 mk7 at the right dosage and duration was capable of raising testosterone levels. You could also look atestradiol as well. You would be looking at "before" and "after" blood tests.

Vitamin K2 directly inhibits new estrogen synthesis

https://www.ncbi.nlm.nih.gov/pubmed/15763078

Interesting. About 4 months ago I supplemented k2 mk7 for about 2 weeks but stopped because there was no improvement to my libido/ED problem. Now very recently I had blood work done by an endocrinologist and everything was in normal range except I had zero estrogen. None at all. He had never seen this before.

He then pointed out this study on Gonadal steroids:www.nejm.org/doi/full/10.1056/NEJMoa1206168 which concludes:

Quote

Androgen deficiency accounted for decreases in lean mass, muscle size, and strength; estrogen deficiency primarily accounted for increases in body fat; and both contributed to the decline in sexual function

So I had a small amount of hope for improval (because for the first time in 10 years someone found something) but this might explain my anomaly.

If it isnt broke dont try to fix it. I feel they took a step back with this new page design.

5 hours ago, geta said:

Interesting. About 4 months ago I supplemented k2 mk7 for about 2 weeks but stopped because there was no improvement to my libido/ED problem. Now very recently I had blood work done by an endocrinologist and everything was in normal range except I had zero estrogen. None at all. He had never seen this before.

If someone was going to look at this objectively, (meaning having no interest in k2) I would be pretty surprised something you took for a span of 2 weeks, affected a blood test 4 months later.
That would be a pretty potent effect. How much k2 were you taking?
That is abnormal having zero estrogen. I have never seen that either.
What was your testosterone?
looking at k2s effect on blood vessel health based on studies, 2 weeks is a very limited time to make any statistical difference. This also is dependent on dosage.

Has anyone thought to just supplement testosterone?

I was about to a few years ago when seeing 2 different doctors but went down the gastro path instead......and here I still am

Compound pharmacies can make it up I believe. If that doesnt do anything Im not sure what will....

12 hours ago, guitarman01 said:

If it isnt broke dont try to fix it. I feel they took a step back with this new page design.

If someone was going to look at this objectively, (meaning having no interest in k2) I would be pretty surprised something you took for a span of 2 weeks, affected a blood test 4 months later.
That would be a pretty potent effect. How much k2 were you taking?
That is abnormal having zero estrogen. I have never seen that either.
What was your testosterone?
looking at k2s effect on blood vessel health based on studies, 2 weeks is a very limited time to make any statistical difference. This also is dependent on dosage.

200g 1x daily. Here's the exact product: https://www.amazon.de/dp/B014RIHYFE?ref_=pe_1365651_54849071 . Since my first post I've asked my endo about this and he says there's nocausal relationship possible.

Testosterone was864 ng/dL, above avg for my age (late 30s).

This forum is very distracting to me now for use on desktop. Less space for posts. It makes me not want to use it. The old one had its quirks, but it was better than this as far as usable space and theme.
I started a poll if you feel the same way.

[Edited link out]

people just need to try things in a systematic way, post results before and after they try whatever they are doing and write a little bit about what that thing did for them, permanent or temporary fix etc.

So much talk about nothingness

Anyone in the uk want to attend a meeting in London on the 7 March and or provide a case history for consideration.

This time aroound we need to concentrate on the sexual sides.

PM me

13 hours ago, Iamme. said:

people just need to try things in a systematic way, post results before and after they try whatever they are doing and write a little bit about what that thing did for them, permanent or temporary fix etc.

So much talk about nothingness

So when I come across information like this,

Isotretinoin increased carotid intima-media thickness in acne patients

or this, (because multiple people including yourself have had concerns about kidney function)

Vitamin K Dependent Protection of Renal Function in Multi-ethnic Population Studies

(Also realize these studies are both recent as two years ago because they are just finding out about some of this)

or finding links to multiple drugs,

I should choose to withhold this information because some individuals don't deem it as important or were never really paying attention?

I'm sorry but some people are absolutely sleepwalking on here.
I normally don't think too highly of myself, but I might be one of the better chances some of you got, and it might never come around again.

On 2/9/2018 at 8:09 PM, 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 now, hatetane said:

On 2/9/2018 at 8:09 PM, 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.

Flynn can you please make contact with me - urgent

On 2/10/2018 at 7:14 PM, Dubya_B said:

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.

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.

.

Dubya - can you email me please.

This is what I'vementionedbefore that I thought might be a possibility. One of the earliest warning signs.
This would be microcirculation. The tiniestblood vessels that feed the hair follicles.
Obviously Accutane having some 5ar inhibiting property, its effect on hair loss would be different.
The same principleapplied here could be systemic.

New research suggests that while DHT is definitely implicated in hair loss, it may actually be the long-term accumulation of scalp fibrosis andcalcification, which slowly starves our follicles of oxygen and causes our hair to thin.

4 years passed since my last pill. I took 40mg/day for two months in 2014 Jan/Feb.
Stopped after I realised that I could not achieve an erection.
Other symptoms started after I stopped Accutane.

This is the list of my problems since:

-ED: Still no connection between penis and brain.
I can not move it in flaccid, it is just attached to my body.
I do have morning woods, sometimes hard rock, sometimes weak.
The top of my penis is not full, the blood can not circulate till top when erected also in flaccid state.
There is a small dent in penis muscle at the bottom (between testicles and penis area) in flaccid, dissappears when erected.
I dont have prostate tingle feeling.
I dont have libido.
The flaccid state get worse after urinate or shit, used to be the opposite.
There are some times where I get horny or flaccid state gets bigger but does not last long,
The changes are so rapid, overall ED status changes in hours.
Update: I lost the pleasure of ejaculation. It is dull.
- Tinnitus: still there, biggest concern after ED.
- Vision problems: floaters are gone by 99%. But I am still night blinded and have some visual snow and double vision.
- Tremors: Gone
- Weak urine: still there sometimes. Definitely the prostate is involved in all this.
- Hair: I lost lots of hair. But the thickness improved somehow after 4 years. I can say I dont have menopause hair anymore.
- Dry eyes, nose, mouth: I never had these.
- Panic attacks, anxiety, suicidal state: Gone
- Energy: Better, just as pre accutane.
- Flexibility: Improved, %80

I tried estrogen blockers but they gave me gyno. I tried testogel but it gave me anxiety.
I have a twin brother and my body looks older than him. This medicine aged me fast forward for 25 years I think.
I feel lucky that mentaly I am ok and have no gastro issues. I eat what I want.
I cut sugar for 6 months but it helped nothing.

Uk - isotretinoin meeting in London on 7th March - anyone up for it?

6 hours ago, IhateAccutane said:

Vision problems: floaters are gone by 99%.

So you had eye floaters and they went away on their own? That's good news at least.
So your main symptoms currently are Ed and tinnitus?

Muscle weakness, nerve connections, blood flow. I think they all could be related.
My tinnitus has seemed permanent. But im not sure if it really is, or would even qualify as tinnitus.

Someone came on here awhile back and had been diagnosed with collapse of the sinus structure.
The doctor threw some antibiotics and steroids at it I believe. Probably didnt help, maybe even made things worse. idk he never came back on.

I envision muscle weakness of the entire face, skull, even in the brain, that regulate blood flow.
It all might start in the muscles.

New cause discovered for arterial stiffness, a contributor to cardiovascular disease

https://www.sciencedaily.com/releases/2015/05/150511125358.htm

Previous studies of aortic stiffness have focused on changes in structural proteins that alter the properties of vascular walls causing them to become rigid. Now, researchers have determined that smooth muscle cells, which line the interior of vascular walls, are a major contributing factor to vascular stiffness, one of the major causes of hypertension.

What is a muscle protein doing in the brain? The Biochemist Blog

On 2/28/2018 at 5:19 PM, hatetane said:

Flynn can you please make contact with me - urgent Dubya - can you email me please.

whats up bro. It won't let me message you for some reason. Maybe the new website format.

Never heard of eye floaters disappearing, they may drop but disappear??

Interesting when you look up floaters how it mentions theyre an age related thing, some of us got them overnight after tane along with feeling like a 90 year old with the aching body, stiffness, thin hair, extreme fatigue etc.

Why though??.....gut, liver, endocrine, heart, kidney......what kicked it off?.....ohh to have the answer to that question.....