----

As of right now im contemplating if to pursue the "rule out everything else that could cause symptoms" or to just focus on accutane. Or to work on both 50/50.

Because one theory is that all our issues are accutane and accutane alone, but other people get our exact same issues for other reasons. So accutane might have simply just made us weaker in some ways which let other things get hold and cause their own issues.

best method is probably the 50/50 route where working on figuring out wtf accutane did while at the same time also just perfecting life and testing everything else to such a big degree that what you end up with is a result that you are either perfect again or the sole reason has to be accutane.

If you catch my drift, only when every other aspect is perfect for a long period can we really know if accutane is the cause. Living optimally and getting all those habits and the willpower alone will require perhaps years for some people and reversing accutane can take years as well.

Its a long journey ahead but hey im only 20 and if i give up then i have to endure living like a sick person for a lifetime..

I just orient my life around the healing journey, career goals shifted from graphics design/filmmaking to doctor/personal trainer/nutritionist/researcher.

Life shifted from eating whatever whenever, drinking and smoking to a healthy life with workouts and supplements etc.

In some ways accutane shifted me into a better way of living, i no longer care for superficial things like reputation, money and looks etc. And i care about health, family, helping others, saving the planet and just being a happy nice kind person. Where as i was rather a douchebag that only did reckless things and partying before..

The only downside is that unless we fix this we wont reap the benefits of healthy perfectionist living because we will be doing everything right and still be sicker than the people who dont give a fuck.

Excuse my language, its for style and making a point.

I often get this by ignorant people: "Well if you eat so healthy and care so much about lifestyle and supplements how come you are so sick and weak and other people who live normallyare not"

I also want to blog/vlog the whole journey but i have limited time and energy to spend on both sides. Spending time on filmmaking and organizing it, editing it and also blogging the journey is a big hassle outside of all the work i already spend on research and such.

But i'll start small and work my way up. I'll just start with summarized "diary" versions of how im recovering with doing different things and ill probably get a GoPro or something since its so small and can also film timelapses. So i could film my research sessions as well and make some nice documentary in the future. If i dont have the energy to do it now ill simply put it on harddrives with timestamps so i know what order stuff was filmed in and i can edit it in 5 years or so lol

Hey there guys just wanted to say I'm no scientist and know nothing about biology but has anyone triedspending more time at the beach? Soaking up the natural minerals, negative ions, healing benefits and natural vit D? I felt really good after the second time at the beach and going to take advantage of summer tospend more time there.

^ I spent all summer in parks and in the sun, and it does work positively towards your sense of well being, however it's just not the same as it used to be with this post tane mental cloudiness. Can't really feel the trees anymore or the sun. I lay out there all day and I have to put lotion on, because i know i'll burn, but I really don't feel the actual power of the rays. Not to mention my vision is shit after accutane so I can't enjoy blue skies or night stars anyway. I remember spending all day outside in the sun, being active, and taking the best naps in the afternoon, wake up to munch on good food, and still fall asleep at night and go to school in the morning. That life is completely gone. 1. my schedule shifted immediately post tane, day-night reversal 2. i haven't taken a nap in 8 years, and if it is indeed a "nap" my body counts it as my offical sleep and my day and schedule gets prolonged into the next day. Also, my new post tane sleep is completely different, eyes close, i go through rem dream sleep (of which i remember now, every single day) and then my eyes open. There's no puffy face, no baggy eyes, yawning. It's just eyes close, eyes open. The only time I get the baggy eyes or red eyes, is if my rem sleep is interrupted or cut short. I think being well rested is a thing of the past to be honest. And that's a HUGE part of the repair process for the body. We're like a candle burning at both ends whereas most people go through their lives steadily declining.

I know...I really can't go into detail over this small stuff, but this drug is seriously fucked up, they have no idea. I just gotta vent sometimes. But, we got this. I'm gonna start pulling my share of the work here soon. I wont procrastinate any longer.

16 minutes ago, macleod said:

^ I spent all summer in parks and in the sun, and it does work positively towards your sense of well being, however it's just not the same as it used to be with this post tane mental cloudiness. Can't really feel the trees anymore or the sun. I lay out there all day and I have to put lotion on, because i know i'll burn, but I really don't feel the actual power of the rays. Not to mention my vision is shit after accutane so I can't enjoy blue skies or night stars anyway. I remember spending all day outside in the sun, being active, and taking the best naps in the afternoon, wake up to munch on good food, and still fall asleep at night and go to school in the morning. That life is completely gone. 1. my schedule shifted immediately post tane, day-night reversal 2. i haven't taken a nap in 8 years, and if it is indeed a "nap" my body counts it as my offical sleep and my day and schedule gets prolonged into the next day. Also, my new post tane sleep is completely different, eyes close, i go through rem dream sleep (of which i remember now, every single day) and then my eyes open. There's no puffy face, no baggy eyes, yawning. It's just eyes close, eyes open. The only time I get the baggy eyes or red eyes, is if my rem sleep is interrupted or cut short. I think being well rested is a thing of the past to be honest. And that's a HUGE part of the repair process for the body. We're like a candle burning at both ends whereas most people go through their lives steadily declining.

I know...I really can't go into detail over this small stuff, but this drug is seriously fucked up, they have no idea. I just gotta vent sometimes. But, we got this. I'm gonna start pulling my share of the work here soon. I wont procrastinate any longer.

The parks aren't the same as the beach

i tried looking up as to why I felt so good and slept really well last night after a day at the beach yesterday and found this....

Everyone:

Use Evernote for storing & compiling research.

Organize everything by tags, not notebooks.

As an example, if the informationrelatesto accutane & detoxification, use something like "accutane detox"

If you read a story about someone curing themselves from accutane by doing X treatment, use "accutane testimonial" or "accutane cure" as well as a tag for the cure: like "accutane St. John's Wort"

This is a fantastic way to store everything and refer to it later.

@Relentless1k

" best method is probably the 50/50 route where working on figuring out wtf accutane did while at the same time alsojust perfecting life and testing everything else to such a big degree that what you end up with is a result that you are either perfect again or the sole reason has to be accutane. "

I've gone down the route of "fix everything and hope for the best" but to no avail.

My lesson learned is "FOCUS ON THE ACCUTANE DAMAGE"

Detoxify it from the body, take SJW, take taurine, heck, drink ethanol if you have to. I've now reached a point where I don't think optimal lifestyle & nutrition can completely heal us. It MAJORLY helps but doesn't completely restore us back to homeostasis. More targeted methods are required. Evidence continues to mount that our genes are not just continually alteredfor no reason. SOMETHING is STILL influencing them. They are not just "stuck."

This is just going to sound stupid... but after reading this paper 3 more times...   http://jn.nutrition.org/content/121/11/1714.full.pdf

Has anyone simply tried high dose Methionine?  This IS the precursor to Taurine. It stands to reason, that if the body is trying to protect itself from accutane, and raising its liver levels of methionine and taurine during treatment, we should help it out?  Massive amounts of each are pissed away during treatment (methionine, taurine, sulfur).  What happens if we run out before the treatment is over?

methionine is needed to produce cysteine... which is used for brittle hair problems

is needed for collagen synthesis... to keep tendons and skin elastic and firm.

Sulfur in general is needed for a lot of our symptoms.

I dont know about the rest of you... but i cut very easily now. if im working, and i scrape or hit my hand with a tool or something, my skin instantly starts bleeding.   

Interesting article from thiis year.  

Backup system that helps sustain liver during crisis discovered

  http://www.sciencedaily.com/releases/2015/03/150320133114.htm?utm_source=feedburner

Ok so the Theory still is... Accutane depletes body of  methionine by upregulating GNMT,  and stopping our ability to make taurine, which is a main conjugate for excess Vitamin A metabolites. This depletion not only stops us from detoxifiying, but also keeps us in a "fasting state."  Think of this as a safe mode for our bodies.   We get stuck in this loop.

It made me remember this word: AUTOPHAGY

From the main FOX01 Accutane paper  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219165/   :

Severe starvation may trigger FoxO1-mediated autophagy and atrophy that break down protein for energy supply, the mechanism that underlies the loss of muscle mass and glycemic control under insulin resistance. It is well known that FoxO1 is a key transcription factor of starvation. Thus, FoxO1 plays a key role in the carbohydrate/lipid metabolic switch in skeletal muscle during fasting/feed cycle. Hyperactivated FoxO1 induces autophagy-related protein degradation through atrogin 1 and muscle-specific RING finger protein 1, which causes atrophy and muscle loss which disturbs metabolic homeostasis (Fig. 6).¹²

In summary, isotretinoin-induced upregulation of FoxO may impringe an artificial œfasting state on muscle metabolism switching to catabolic events in muscle cell homeostasis which may very well explain isotretinon-associated myalgias and increases in CPK due to muscle cell degradation.

...... so this says that Accutane keeps us upregulated in a   "FOX01 fasting state"   Our SAM/SAH ratios stay messed up even after stopping treatment.

Here is a pic of what accutane does,   this shows a muscle cell wasting away.   but maybe it could be a sebocyte oil gland just the same... not able to proliferate or grow. 

How can this be fixed????

 On the right:   Accutane depletes methionine ---> alters our SAM/SAH ratios by depleting the sulfur amino acids in our bodies. 

On the Left:   Reintroduction of MET(methionine) ---> fixing our SAM/SAH ratio ---> allows us to detoxify... stopping the AUTOPHAGY/ quasi-fasting state

However, there were 2 major unanswered questions. First, and perhaps most important, we did not know which metabolites or nutrients, when insufficient, could trigger NNS-autophagy. Second, we did not know the pathways through which this form of autophagy was regulated. The robust induction of autophagy in cells transferred to minimal growth media (from nutrient-rich media) allowed us to investigate whether the addition of specific metabolites could prevent autophagy. Surprisingly, we found that adding back a single amino acid, methionine, was sufficient to potently block such autophagy. Other amino acids, including leucine and glutamine, which have been linked to the regulation of TORC1 activity, had virtually no effect. We then determined that the downstream metabolite of methionine, S-adenosylmethionine (SAM), was responsible for this effect of methionine (Fig. 1). SAM is a central metabolite that serves as a methyl donor for a wide variety of metabolic transformations that result in the methylation of proteins, lipids, and nucleic acids. These methylation modifications are thought to play important roles in cell growth and regulation. We therefore screened non-essential yeast methyltransferase enzymes to determine if any of them were required for SAM-mediated inhibition of autophagy. Our screen identified Ppm1, a conserved methyltransferase enzyme that methylates the C-terminal leucine residue of a major protein phosphatase enzyme, PP2A (Fig. 1). Cells lacking Ppm1 (LCMT1 in mammals) were unable to respond to methionine addition and thus methionine could no longer inhibit autophagy in this mutant.

11 hours ago, trantran83333 said:

Hey there guys just wanted to say I'm no scientist and know nothing about biology but has anyone triedspending more time at the beach? Soaking up the natural minerals, negative ions, healing benefits and natural vit D? I felt really good after the second time at the beach and going to take advantage of summer tospend more time there.

 

You are spot on IMO. Taking a supplement can't match it. It's also metabolised by the liver first, can cause GI issues etc. Id only take it if you're found deficient on blood work AND have trouble accessing the sun and getting levels up that way.

BTW, Does anyone find they react differently to the sun after Accutane?

I still feel good in the sun , but I feel I don't get the same amount of benefits as I used to, ANDalso don't tan nearly as easily.

D is made inthe skin, (onceexposed to UV). Melanin as well.

Accutane changes our skin properties permanently... Maybe it also somehow affects the skins ability to create vit D3 and melanin ?

17 hours ago, tryingtohelp2014 said:

Ok so the Theory still is... Accutane depletes body of  methionine by upregulating GNMT,  and stopping our ability to make taurine, which is a main conjugate for excess Vitamin A metabolites. This depletion not only stops us from detoxifiying, but also keeps us in a "fasting state."  Think of this as a safe mode for our bodies.   We get stuck in this loop.

It made me remember this word: AUTOPHAGY

 

From the main FOX01 Accutane paper  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219165/   :

Severe starvation may trigger FoxO1-mediated autophagy and atrophy that break down protein for energy supply, the mechanism that underlies the loss of muscle mass and glycemic control under insulin resistance. It is well known that FoxO1 is a key transcription factor of starvation. Thus, FoxO1 plays a key role in the carbohydrate/lipid metabolic switch in skeletal muscle during fasting/feed cycle. Hyperactivated FoxO1 induces autophagy-related protein degradation through atrogin 1 and muscle-specific RING finger protein 1, which causes atrophy and muscle loss which disturbs metabolic homeostasis (Fig. 6).¹²

In summary, isotretinoin-induced upregulation of FoxO1 may impringe an artificial œfasting state on muscle metabolism switching to catabolic events in muscle cell homeostasis which may very well explain isotretinon-associated myalgias and increases in CPK due to muscle cell degradation.

 

 

...... so this says that Accutane keeps us upregulated in a   "FOX01 fasting state"   Our SAM/SAH ratios stay messed up even after stopping treatment.

 

 

Here is a pic of what accutane does,   this shows a muscle cell wasting away.   but maybe it could be a sebocyte oil gland just the same... not able to proliferate or grow. 

 

 

How can this be fixed????

 

 On the right:   Accutane depletes methionine ---> alters our SAM/SAH ratios by depleting the sulfur amino acids in our bodies. 

On the Left:   Reintroduction of MET(methionine) ---> fixing our SAM/SAH ratio ---> allows us to detoxify... stopping the AUTOPHAGY/ quasi-fasting state

 

However, there were 2 major unanswered questions. First, and perhaps most important, we did not know which metabolites or nutrients, when insufficient, could trigger NNS-autophagy. Second, we did not know the pathways through which this form of autophagy was regulated. The robust induction of autophagy in cells transferred to minimal growth media (from nutrient-rich media) allowed us to investigate whether the addition of specific metabolites could prevent autophagy. Surprisingly, we found that adding back a single amino acid, methionine, was sufficient to potently block such autophagy. Other amino acids, including leucine and glutamine, which have been linked to the regulation of TORC1 activity, had virtually no effect. We then determined that the downstream metabolite of methionine, S-adenosylmethionine (SAM), was responsible for this effect of methionine (Fig. 1). SAM is a central metabolite that serves as a methyl donor for a wide variety of metabolic transformations that result in the methylation of proteins, lipids, and nucleic acids. These methylation modifications are thought to play important roles in cell growth and regulation. We therefore screened non-essential yeast methyltransferase enzymes to determine if any of them were required for SAM-mediated inhibition of autophagy. Our screen identified Ppm1, a conserved methyltransferase enzyme that methylates the C-terminal leucine residue of a major protein phosphatase enzyme, PP2A (Fig. 1). Cells lacking Ppm1 (LCMT1 in mammals) were unable to respond to methionine addition and thus methionine could no longer inhibit autophagy in this mutant.

Excellent post, @tryingtohelp2014

Quoting the entire thing so it's carried to this page.

Realistically, how much methionine would you estimate would make a difference? They sell 500mg capsules, commonly.

Be aware that a single ounce of meat typically has 200-300mg of methionine.

Are you also taking SAMe in supplemental form?

Also, be aware that SAM is a natural inhibitor for the MTHFR enzyme. If methylation goes too fast, SAM will naturally increase the transulfuration pathway to lower homocysteine so the cycle can't continue. So, if we are wrong and we don't need the extra methionine, we could be creating too much SAM by transmethylating and this could inhibit the MTHFR enzyme, which would not be good. How do we determine if we actually need more methionine or SAM?

--

In regards to being stuck in a sort of fasting state (hyperautophagy):

Maybe we shouldn't focus on reversing the effects of FoxO1 upregulation by trying to block autophagy with methionine etc but rather, we should try to reverse the FoxO1 upregulation directly. I saw in that very same accutane & FoxO1 paper that lithium & antidepessants can decrease FoxO1 gene expression indirectly by decreasing FoxO3a levels. Didn't someone recently mention that they had great results with being on an SSRI? I wouldn't recommend going that route. I'd choose high-dose lithium, instead.

"Antidepressant treatment seems to lead to an increase in neurogenesis, which is chronologically seen during the same period as the clinical improvement.²⁴¹ Severe acne and acneiform eruptions have been observed with high doses of tricyclic antidepressants and lithium therapy. In brain of mice, lithium significantly decreased FoxO3a levels.²⁵⁵As already mentioned, FoxO3a activates the promoter of FoxO1 and is an important inducer of FoxO1 gene expression.¹¹ The acneigenic effect of lithium therapy may be related to a lithium-induced nuclear deficiency of FoxO1 by suppression of the FoxO1 promoter. In mice, elevated serotonergic activity increased Akt-mediated phosphorylation of FoxO1 and FoxO3a in various brain regions resulting in nuclear deficiency of FoxO1 and FoxO3a.²⁵⁶ FoxOs in brain of rodents are intensely involved in the regulation of behavioral manifestation.²⁵⁶ Upregulated serotonin levels by antidepressants reduce nuclear concentrations of FoxO1 and FoxO3 in neuronal cells. FoxO1-deficient mice displayed reduced anxiety, whereas FoxO3a-deficient mice presented with a significant anti-depressant-like behavior.²⁵⁶ Thus, elevated nuclear content of FoxO1 and FoxO3a by isotretinoin treatment in the human hippocampus and hypothalamic areas of the brain may explain depression and mood changes observed with isotretinoin therapy in some susceptible individuals.^241"

It's interesting to see the hypothesis that acne is caused by nuclear deficiency of FoxO1 proteins and isotretinoin is used to upregulate FoxO1 proteins to correct the imbalance but it goes overboard and causes other issues. Anyone have any other opinions on how we could downregulate the FoxO1 genes besides antidepressants & lithium? I should also mention that my hair analysis from Doctor's Data showed very low levels of lithium so I started supplementing lithium orotate. Perhaps my body was trying to naturally downregulate FoxO1 activity by burning through my lithium (yet another way we could become depressed). I am going to start back up. Lastly, I should mention that niacin (flushing) cured ALL of my depression in about 11 days at 3,000mg per day. I personally used the flushing kind. The effects didn't last, though. I am going to do it again but with non-flushing niacinamide. Others should try. Look up Mercola & Dr. Saul's interview on youtube about niacin. Very safe. No need to worry about liver damage.

--

Seems that upregulation of FoxO1 proteins also screws up the HPA axis and especially the pituitary gland.

"Isotretinoin's effect on the CNS is mediated by FoxO1 upregulation. in the hypothalamus FoxO1 inhibits neurogenesis associated with the risk of mood changes. FoxO1 suppresses the expression of proopiomelanocortin (POMC) and carboxypeptidase E (Cpe). This results in reduced formation of ±-melanocyte stimulating hormone (±-MSH) and general suppression of the hypothalamic-pituitary-axis (HPA) with decreased pituitary hormone secretion."

Has anyone tested their MSH levels? I'd be curiuos to compare MSH levels among accutane users. MSH controls cytokine release and pituitary function. 90%+ of illnesses have inflammation behind them. This inflammation is cytokine mediated. The master regulator is MSH as it regulates all hormones via the pituitary. A level of 35-81 pg/ml is ideal. Lab Corp #010421 can be used to test.

--

Are you still supplementing manganese? What about molybdenum?

1 hour ago, yetanotheraccutanevictim said:

 

It's interesting to see the hypothesis that acne is caused by nuclear deficiency of FoxO1 proteins and isotretinoin is used to upregulate FoxO1 proteins to correct the imbalance but it goes overboard and causes other issues. Anyone have any other opinions on how we could downregulate the FoxO1 genes besides antidepressants & lithium? I should also mention that my hair analysis from Doctor's Data showed very low levels of lithium so I started supplementing lithium orotate. Perhaps my body was trying to naturally downregulate FoxO1 activity by burning through my lithium (yet another way we could become depressed). I am going to start back up. Lastly, I should mention that niacin (flushing) cured ALL of my depression in about 11 days at 3,000mg per day. I personally used the flushing kind. The effects didn't last, though. I am going to do it again but with non-flushing niacinamide. Others should try. Look up Mercola & Dr. Saul's interview on youtube about niacin. Very safe. No need to worry about liver damage.

--

 

 

 

 

Holy shit dude, you just described my Doctors Data hair test i just got back last week.

Extremely low lithium!  

Yeah i dont know what to expect on methionine supplementation.  I honestly think it cant hurt, especially if you take it with the b6, b12 , folate. Right... egg whites contain over 1000mg of methionine.    we probably need a lotof it to feel anything.   maybe the first step was still to take taurine to get our bile acids working again... so we can start absorbing it anyway.

 Everyone should get a 23andme test to see if they have that cbs mthfr problem.

everyone must,must watch this in full. I think this could pertain to alot of the long term side effects that alot of us are dealing with. and maybe another avenue to look at forthose desperate for a solution.

51 minutes ago, guitarman01 said:

everyone must,must watch this in full. I think this could pertain to alot of the long term side effects that alot of us are dealing with. and maybe another avenue to look at forthose desperate for a solution.

Sounds interesting enough though I can't help but wonder when I read that doses over 10.000 IU if not managed properly may cause irreversible damage of renal function. It leads me to believe that I obviously didn't manage my intake of Vit A properly when on Accutane......what have I "permanently damaged" as a result??......just my brain perhaps, who knows as there was no one there to help!!?

I didn't have a doctor or dietitian monitoring me nor was I advised to....thanks doctor for not doing your job properly!!!

I'm not going to go out and pump myself full of Vit D in the hope that it works, we really need someone who knows what they're doing, someone who can help advise on how much to take and when. I'm still trying to work out if Methionine or Taurine have any lasting effects - not to mention the 2950 other supplements that are discussed in these pages.......

Not much room left in the cupboard for any more supplements in my house. Interesting video though - thanks for sharing, I'd be cautious though trying to manage Vit D intake by myself, I would consult ( was about to say doctor...nah ) a health practitioner to get an informed view on how to manage this.

it is easy enough to get periodic vitamin d blood test, blood calcium, pth levels checked. numerous post all over the internet that many people take 25k to 30k iu of d3 per day and still stay in normal range.

Also how many of you have tried a plant based vitamin d3 or even d2 supplement? almost every other d3 supplement out there is based on sheep's oil from their wool. That I myself has always had a problem with it giving me severe acid reflux and made me feel irritable. just now trying out a plant based d3 from algae and so far no negative side effects at higher doses. Think about it maybe we just cant process the d3 from the sheep oil, it could be that simple. i know my skin looked better and i felt pretty good after drinking almond milk awhile back, couldnt figure it out. then I see they use d2 in that milk to keep it vegan. also calcium supplements gave me problems when i tried them awhile back. I still get muscle twitches from taking a normal dose calcium for just a short amount of time. maybe because lack of vitamin d or it getting properly used to absorb the calcium.

FOXO1 Mediates Vitamin D Deficiency

also crucial in proper sweating, you have receptors in your sweat andoil glands

hell now they are saying vitamin d deficiency causes cystic acne in the first place, and what did we all do? ingested massive doses of its antagonist.

th17, cytokines, fox genes,insulin,inflammation,serotonin,dopamine.nerve function,bones, muscles, immune system,sun sensitivity,hair loss it all goes back to vitamin d. What would be the strongest nutrient on the planet that provides life itself? the sun(which is the main natural source of vitamin d)

really everyone needs to watch that video I just posted, it goes alot deeper then lets all just take high dose vitamin d supplements

Nothing beats the sun, but I wonder if accutane damaged our skins ability to synthesize vitamin D

I'm a bit suss on takingmassive oral mega doses of liver metablized D3.

Is it just me or is there something wrong with the quote functionality? Post shows wrong quotes.

2 hours ago, Roland1968 said:

Is it just me or is there something wrong with the quote functionality? Post shows wrong quotes.

 

 

If the posting function is messed up for you, go to history and clear EVERYTHING. I've found that works for me (at least for Chrome browser).

As for the vit D, I would recommend against mega-dosing it BUT I haven't watched the video, yet. If you decide to do it, monitor the blood biomarkers mentioned above and monitor your 25 hydroxy vitamin D AND your 1,25 hydroxy vitamin D. Some chronic diseased patients can get worse from supplementing D while inflamed(lyme disease pts as an example).

Also, there's no mechanism for the body to stop taking in D if it doesn't come from the sun. If we have too much from the sun, we stop converting it.

We can't overdose on sunlight vit D but we CAN insupplemental form.

I'm really struggling at the moment. As soon as I realise all my issues were started because of this drug I get so stressed out knowing I don't have a clue what is going on. 10 years and counting. I just don't know how to go on from here. I can't deal with this chronic fatigue for the rest of my life. Happy 2016 :/

On 9 December 2015 at 05:21:41, tryingtohelp2014 said:

 

from your article:

 "Furthermore, the isotretinoin-induced decrease of IGF-1 serum levels may impair IGF-1/PI3K/Akt-mediated nuclear export of FoxO1. Moreover, IGF-1 is regarded as an androgen-dependent stimulator of 5±-reductase activity.³⁸ In fact, experimental evidence has been provided for decreased androgen 5±-reduction in skin and liver of men with severe acne after oral isotretnoin treatment.³⁹ The isotretinoin-induced decrease of IGF-1 may reduce the conversion of less potent testosterone to the more potent dihydrotestosterone (DHT)"

 

So here it states accutane causes all of the problems by:  upregulating FOXO1 ---> upregulated FOXO1 supresses IGF-1 and PI3K/AKT --->  drying out of the skin.   this also directly ties us with the finesteride people by reducing 5AR.

 

So now how to fix this in  the exact reverse?   stimulate or upregulate the PI3K/AKT ---> leading to increased IGF1 ----> leading to a nuclear mediated/ suppressed FOXO1

 

FoxO1 is an important metabolically regulated AR corepressor and binds to the TAD, where it disrupts p160 coactivator binding and suppresses N-terminal/C-terminal-interaction, which is most important for AR transcriptional activity (Fig. 2A).³² The AR repressive function of FoxO1 is attenuated by increased growth factor signaling with activation of the PI3K/Akt cascade.^33,34

 

cross reference this with PI3K/AKT IGF1 promoters and i find this!:

http://onlinelibrary.wiley.com/doi/10.1002/eji.201242450/full

The PI-3 kinase (PI3K)/Akt pathway is instrumental for this form of metabolism, since this pathway regulates the cellular uptake of glucose [[11]]. It is therefore interesting to note that taurine activates the PI3K/Akt pathway [[12]] and reduces blood glucose levels in diabetic rats [[13]]. Hence, taurine may not only help providing space for aerobic glycolysis, but is also fueling the system with enough nutrients by stimulating the PI3K/Akt pathway. Increased protein and lipid synthesis are essential for proliferating cells, and both processes are happening in the cytosol and associated membranes, and thereby add to the increased space requirement in activated T cells. Taut and taurine metabolism may function to regulate an intrinsic T-cell size checkpoint.

The article by Kaesler et al. [[7]] portrays taurine and its transporter Taut as a potential drug and drug target, respectively. By changing taurine levels, it may be possible to specifically affect T-cell responses (Fig. 1). Increasing taurine levels by exogenous administration may be expected to enhance effector and memory T-cell responses. Indeed, taurine has been shown to enhance the rejection of tumor cells in a mouse melanoma model [[14]]. Conversely, blocking taurine uptake may promote T-cell death by negatively regulating PI3K/Akt anabolic signaling. Such an approach could be attractive for the treatment of autoimmunity and in particular organ transplantation. In the latter situation, short-term inhibition of taurine transport immediately after transplantation may be able to eliminate proliferating organ-specific T cells, effectively inducing T-cell tolerance.

 

also mitochondrial dysfunction chart

 

 

ALL very exciting!!!

 

Just received a new supplement this week called Astaxanthin (a naturally occurring carotenoid). The reason I bought this is one of the guys who partially recovered earlier on this thread, after using RSO (sorted all his sides, bar brain fog/cognitive issues) mentioned this improved his mental clarity quite significantly (at 12mg/day) so I thought I'd give it a go. 

Having looked at a few studies to see if I can see any reasons why this might have been a benefit, I've noticed Astaxanthin actually upregulates PI3K/Akt.. 

http://www.ncbi.nlm.nih.gov/pubmed/26261486

Might explain why he's found this to be of benefit, so taken along with taurine might yield further benefits. Will update if I notice anything from it. 

3 hours ago, tanedout said:

 

Having looked at a few studies to see if I can see any reasons why this might have been a benefit, I've noticed Astaxanthin actually upregulates PI3K/Akt.. 

 

http://www.ncbi.nlm.nih.gov/pubmed/26261486

 

Might explain why he's found this to be of benefit, so taken along with taurine might yield further benefits. Will update if I notice anything from it. 

I think i really have something, and it relates back to the PI3K/AKt pathway as well.....

Ok going back to this diagram.  This diagram explains the pain that people feel in their joints and muscles due to accutane.  Accutane upregulates FOX01 ---> which upregulates ATG-1 (Atrogin ... this is the new boogeyman for me) ----> which causes a fasting state (youre basically eating away at your muscles for amino acids)  ----> causing the autophagy--->  which causes CPK release, resulting in muscle/joint pain (Myalgia).  

Ok so, researching this ATROGIN ATG-1 i come up with this...

Methionine supplementation has a positive effect on protein synthesis by acting on several factors, and methionine supplementation affects the expression of genes related to growth. Higher mRNA expression in the liver [2] and increased levels of circulating IGF-I are often associated with animals on supplemented diets [3]. Methionine has also been reported to be an inhibitor of enzymes, such as atrogin 1, which participate in degradation via the ubiquitin-proteasome pathway [4].

Moreover, similar to when there is a lack of nutrients, such as amino acids, high temperatures may also be blamed for promoting proteolysis. In addition to the effects of increased ROS production on metabolism, stress is also associated with lower IGF-I expression, increased expression of components of the ubiquitin-proteasome pathway [5], activation of transcription factor Forkhead box (FoxO) signaling [6], and autophagy induction [7].

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340924/

THEORY TIME:

This is that "safe mode" i was talking about.  What this says is... when your body is sulfur depleted, it basically thinks its starving(no matter how much food you eat)...this keeps FOX01 upregulated....because sulfur amino acids are "costly" to synthesize (i.e. TAURINE/SAM-E)  Maybe, just maybe this also could be the reason why we have long term side effects after stopping accutane.  Just because we stop taking the drug, doesnt fix this sulfur depletion!!  Our body used up all of the sulfur, and continues to use up sulfur we take in to combat whatever is still deposited inside our livers/fat.  And until we take a corrective amount to break this loop, we'll be stuck. We know for a fact that accutane uses up methionine and its metabolites to detoxify.  http://www.ncbi.nlm.nih.gov/pubmed/1941178     "These findings indicate that dietary CRA has the ability to alter the catabolism of methionine and subsequently influence hepatic transmethylation as reflected by the SAM:SAH ratio".    We also know for a fact that accutane upregulates the GNMT enzyme.... which DESTROYS Methionine.... and this enzyme has been shown to STAY UPREGULATED well after stopping accutane.

Accutane ingestion ---->body mobilizes all available methionine and existing taurine, to conjugate and excrete http://jn.nutrition.org/content/121/11/1714.full.pdf   ---->body runs out of methionine in liver----->body robs muscles of any available methionine /sulfur---->with no available methionine left to conjugate accutane, body then stores accutane metabolites in liver/fat for later excretion----->FOX01 stays upregulated indefinitely in a fasting state due to sulfur deficiency(specifically methionine) ---->resulting in LONG term side effects (*dry skin, joint pain,depression*)

this explains the fasting state again.....

Methionine Inhibits Autophagy and Promotes Growth by Inducing the SAM-Responsive Methylation of PP2A

We have uncovered growth conditions under which the sulfur-containing metabolites methionine and SAM become sufficiently limiting to induce autophagy. Why might cells choose methionine and SAM as a gauge of their metabolic/nutritional state? Sulfur-containing amino acids are very energetically costly to synthesize (Thomas and Surdin-Kerjan, 1997), requiring four equivalents of NADPH simply to reduce one molecule of sulfate to metabolically active sulfide (Figure 2B). Sulfide is then used to synthesize homocysteine, whose carbon skeleton is ultimately derived from oxaloacetate, a TCA cycle intermediate. The methyl group that is appended to homocysteine to form methionine is derived from one-carbon metabolism and the folate pathway, which also consumes significant NADPH (Thomas and Surdin-Kerjan, 1997). Thus, sulfur amino acids are dependent on multiple important metabolic pathways for their synthesis.

Sulfur and its metabolites also form the basis of a metabolic checkpoint for entry into the cell cycle (Unger and Hartwell, 1976). Upon sulfate starvation, yeast cells conserve nutrients and properly arrest their growth to promote survivability (Boer et al., 2008).

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774293/

---->  this is why accutane is used as a chemotherapy drug!!  in the same way yeast cells stop growing, cancer cells also stop growing due to cell arrest, because of sulfate starvation?!

So maybe, the upregulation of FOX01 by accutane isnt primary.... meaning, its really accutane's depletion  of methionine over time, that upregulates FOX01 and keeps it upregulated well after discontinuation causing the long term effects. This could be a solution to the paradox of,  "Well, if accutane isnt stored in our bodies anymore, how can i still experience side effects years later?"   Also could explain the side effects felt by ingesting normal levels of  pro-vitamin A rich foods.  If we dont have anything left to get rid of it, we tax our systems all over again, causing bad sides.

Now the only question is.... what to take and how much?  Do we take straight Methionine? Do we take SAM-E? Do we take Taurine?   do we take ALL THREE?  ... and at what dosage?  do we have to take b6 b12 folate as a precaution against homocysteine? Are there any other substances that can increase methionine potency or recirculation.  

Best case is.... this is a simple methionine/sulfur repletion strategy which would result in FOX01 downregulation and an end to all side effects.

My guess, from anecdotal evidence....is that we're also going to have to conjugate leftover stored metabolites as well, taking more time, but more importantly, causing a re-introduction side effects that we have to deal with by reversing a fatty liver chocked full of accutane.

btw...

Someones Entire thesis on SAM-E and 13 cis retinoic acid....

http://lib.dr.iastate.edu/cgi/viewcontent.cgi?article=4063&context=etd

1 hour ago, IndigoRush said:

I'm really struggling at the moment. As soon as I realise all my issues were started because of this drug I get so stressed out knowing I don't have a clue what is going on. 10 years and counting. I just don't know how to go on from here. I can't deal with this chronic fatigue for the rest of my life. Happy 2016 :/

Get your head out of the sand and start reading posts from your own thread.... we're close!!

Be careful with the Astaxanthin. Studies show it is a potent DHT inhibitor and can possibly mess with 5ar

still going back and fourth on a few different supplements im taking something is really making me feel better, cant pin down what it is yet. been taking 50 to 60mg or (60,000mcg) of biotin per day for the past couple of days. going to neologist on monday and going to get tested forbiotinidaseenzymedeficiency andhomocysteinelevels, any other test anyone can think of?becausewhats wrong with me could be whats wrong with you.

Mild deficiency

Because it is synthesized in the gut, deficiency symptoms of biotin are rare. However they may include weakness, lethargy, grayish skin color,eczema(which may include a scaly red rash around the nose, mouth and other orifices),hair loss, cradle capin infants, muscle aches, impaired ability to digest fats,nausea, depression, loss of appetite,insomnia, highcholesterollevels, eye inflammations, sensitivity to touch,anemia, and tingling in the hands and feet.

Extreme deficiency

Symptoms of extreme biotin deficiency include elevation of cholesterol levels, heart problems, and paralysis. When extreme deficiency is a problem, the liver may not be able to detoxify the body efficiently, and depression may develop into hallucinations. Infants may exhibit developmental delay and lack of muscle tone.

Biotin deficiency could result in a loss of immune function, since animal experiments have shown that biotin deficiency resulted in a decrease in white blood-cell function. Because biotin is essential to the body's metabolic functions, any deficiency could result in impaired metabolism as well.

2 minutes ago, guitarman01 said:

going to neologist on monday and going to get tested forbiotinidaseenzymedeficiency andhomocysteinelevels, any other test anyone can think of?becausewhats wrong with me could be whats wrong with you.

CPK test

IGF-1 test

@tryingtohelp2014

I tested my creatine kinase and it's in the normal range. I have extreme muscle pain. I am 96% sure it's oxalates built up in my tissues. For some reason, I became unable to detoxify oxalates. I know the enzymes involved in oxalate transport are the same ones that transport sulfur.

I like your methionine/sulfur theory. It makes sense BUT we have no way to measure that. We also have no way to determine how much to take or a way to monitor results. One thing I should note is I've beenhaving at least a whole head of cabbage per day for the past few weeks (plenty of sulfur)

@guitarman01For homocysteine levels (Ben Lynch):

"Properly prepare yourself to get your homocysteine level measured.

Ensure the lab handles your blood sample properly.

23 minutes ago, Modeaa said:

 

Fatal rhabdomyolysis after acne therapy: A 20-year old was changed to the retinoid isotretinoin by mouth (40 mg/day; e.g. ISOTRETINOIN-RATIOPHARM), after he had tried various drugs against acne for two years without success. Several weeks later he complained of strong muscle pain after exertion during sporting activity which disappeared after using pain-relieving topical agents. Shortly afterwards, the young man's condition deteriorated increasingly during a demanding one month's Asian trip, during which isotretinoin intake was suspended, to the extent that he experienced respiratory problems when climbing stairs. On the trip home he needed a wheelchair at times. A few days after admission to hospital in Germany he died of heart failure with massive pulmonary oedema. Creatinine phosphokinase (CPK) level was extremely elevated at 82.000 U/l. The musculature appeared softened in places according to the autopsy report. The forensic expert attributed the death to very severe rhabdomyolysis caused by taking the long-acting isotretinoin and unaccustomed physical exertion

http://www.ncbi.nlm.nih.gov/pubmed/16703787

 

supports this.