Destruction of hippocampus neurons and overall hippocampus size is implicated in accutanes depression and suicidal thoughts.

How the PI3K/AKT pathway saves hippocampal neurons...

The main findings of this study are as follows: (1) the expression of pAkt increased markedly in the hippocampus neurons of rats after experimental SAH, and the experimental SAH in this model induced obvious neuronal apoptosis; (2) administration of IGF-1, the agonist of the PI3K-Akt pathway, increased the expression of pAkt remarkably and alleviated neuronal apoptosis significantly in rat hippocampi after experimental SAH; (3) Ly294002, the inhibitor of the PI3K-Akt pathway, decreased the expression of pAkt and aggravated neuronal apoptosis in the hippocampus after SAH. These findings indicate that the neuronal apoptosis in this model of experimental SAH in rats could be alleviated with the activation of the PI3K-Akt pathway and aggravated with its blockage. Hence, the PI3K-Akt pathway may play a crucial role in neuronal apoptosis after SAH, and its activation may reduce the severity of secondary brain injury following experimental SAH.

http://www.annclinlabsci.org/content/41/4/364.full

you can cross reference PI3K/AKT with cholestasis as well....

Peony(paeoniflorin is used in Chinese medicine for cholestasis....

Paeoniflorin ameliorates ANITinduced cholestasis by activating Nrf2 through an PI3K/Aktdependent pathway in rats : PTR

https://pubag.nal.usda.gov/pubag/article.xhtml?id=4569066&searchText=author%3 A"Jiabo+Wang"&searchField=

Why do we have collagen problems? How can we go about fixing that issue?

2 hours ago, tryingtohelp2014 said:

so many things are inter-related here. i believe there is something acting on the FOXO for sure... be it stored in the liver, or in the adipose tissues... or micro amounts stuck to the skin receptors. i think the main thing is to make sure its bio-available copper. maybe the zinc with keep the retinol bound to RBP. maybe a cocktail.

eat a shit ton of cashews...sesame seeds... something with a higher amount of copper than zinc. get it in the circulation and then bind it or destroy it... taurine...vitamin D etc

the very end of this video is what we need to do... so our cells stop getting destroyed. Cu also stimulate the RAS pathway

A Novel Role for Copper in Ras/Mitogen-Activated Protein Kinase Signaling

http://mcb.asm.org/content/32/7/1284.full

have you tried this ?

copper/zinc + ox bile or taurine then ? Ill try that tomorrow if the science is sound.

I love Marmite cashews =)

2 hours ago, tryingtohelp2014 said:

so many things are inter-related here. i believe there is something acting on the FOXO for sure... be it stored in the liver, or in the adipose tissues... or micro amounts stuck to the skin receptors. i think the main thing is to make sure its bio-available copper. maybe the zinc with keep the retinol bound to RBP. maybe a cocktail.

eat a shit ton of cashews...sesame seeds... something with a higher amount of copper than zinc. get it in the circulation and then bind it or destroy it... taurine...vitamin D etc

the very end of this video is what we need to do... so our cells stop getting destroyed. Cu also stimulate the RAS pathway

A Novel Role for Copper in Ras/Mitogen-Activated Protein Kinase Signaling

http://mcb.asm.org/content/32/7/1284.full

ya know, strangely enough, about 2 years after accutane i went through a period where i ate a shit ton of sunflower seeds most days and i got really sick. I just figured id poisoned myself with them.

But for those of us who take Zinc we don't want to induce deficiencies and take no copper right? Chrysler recommends 30:1 zinc : copper ratio.

I used taurine by the spoonful years ago. Years later I stopped using it because it made me feel extremely lethargic and tired. I tried it again a couple days ago and it caused anxiety and insomnia so I wont be able to continue it. : /

Just to add to the anecdotes: I eat copious amounts of sprouted sunflower seeds and pumpkin seeds nearly every day. In addition, I practically live off of pecans and walnuts. They are my replacement for all of the grains I used to eat. I never noticed symptoms worsening as a result.

The only correlations I've noticed between foods and feeling worse are nightshade vegetables (i.e., white potatoes especially) and high-sulfur foods. In regards to the latter, I can generally get away with eating eggs or eating high-sulfur green vegetables. But if I eat both in one day (or an excessive amount of one), my stomach acts up. I start feeling "stiff" joints and generally unsettled all-around. It appears Accutane helped kickstart some sensitivities.

The idea of using Retinoic Acid antagonists is not so far-fetched. They are being researched for treating arthritis and as a male contraceptive.

http://www.oarsijournal.com/article/S1063-4584(13)00653-5/fulltext

Quote

It has been shown that the natural ligand for the Retinoic Acid Receptors (RARs), All Trans Retinoic Acid (ATRA), is deleterious to articular cartilage health and is associated with the breakdown of cartilage in osteoarthritis. Additionally, it has been shown that retinoid levels are increased in the synovial fluid of OA patients. Both natural and synthetic retinoids (RAR agonists) are catabolic to cartilage, block early chondrogenesis and promote chondrocyte hypertrophy via RAR signaling through three RAR subtypes (RAR alpha, beta and gamma). It has been postulated that RAR antagonists may prevent or reverse retinoid-mediated cartilage destruction and a RAR pan antagonist was previously shown to improve clinical scores in the collagen-induced arthritis (CIA) model, albeit with unacceptable adverse effects on testes. We have postulated that the primary beneficial joint effects of RAR antagonists are associated with RARgamma, while the adverse effects on testes are associated with RARalpha. Thus, we have identified a highly selective RARgamma antagonist (LY2813631) to test this hypothesis.

https://www.ncbi.nlm.nih.gov/pubmed/23053561

"Recent work showed that -apo-13-carotenone is also a high-affinity antagonist of all 3 retinoic acid receptors (RAR, RAR, and RAR)."

-apo-13-carotenone is a breakdown product of Beta-carotene and it antagonizes all 3 RA receptors. Problem is, beta-carotene will also convert to ATRA and will cause symptoms. I read somewhere that high doses show adverse events in other studies and they speculate its because of the formation of antagonists. Maybe higher doses favor antagonist production which might be beneficial for us?

Apocarotenals are actually used by the food industry as a natural colorant for foods like yellow cheese and some deli hams and I requested samples from a manufaturer ofTrans-Beta-Apo-8'-carotenal. Although, I dont think this substance is a pure antagonist like 13-carotenone.

Hi guys and gals,

I was only on Accutane for a little over a month. 40 mg per day. I noticed myself becoming super depressed, even more so than the slight symptoms of depression I had had in the past. I took myself off of it after my vision had started to become blurry. That was really troublesome. Now, 4 months after I have stopped, I have noticed my symptoms getting worse. My libido is almost gone. Even when I try to do it myself I notice that it's not the same as before. Orgasms are bland and I'm not as sensitive as I once was to stimuli. I'm single, but you know your own body enough to know how you used to be. I am extremely depressed, to the point of apathy. I don't enjoy things I used to enjoy before. To be happy or sad even I find that I have to make an effort to feel these feelings that came naturally before. I find my mind constantly foggy and confused at times. I find myself having trouble facing reality. I found myself googling my symptoms post Accutane which lead me to this blog. Has anyoneyou found any relief in their symptoms? I find these blogs helpful and comforting to know that I'm not alone. I fear I will never be the same person as I was before. Only a shadow of what I once was. There must be something in this world that can help me be me again.

Quote

Thus, topical use of a RAR antagonist as an antidote to block the cutaneous toxicity of Accutane should greatly improve patient compliance.

13-cis-retinoic acid alters the cellular morphology of slice-cultured serotonergic neurons in the rat.

23 hours ago, tryingtohelp2014 said:

Destruction of hippocampus neurons and overall hippocampus size is implicated in accutanes depression and suicidal thoughts.

How the PI3K/AKT pathway saves hippocampal neurons...

The main findings of this study are as follows: (1) the expression of pAkt increased markedly in the hippocampus neurons of rats after experimental SAH, and the experimental SAH in this model induced obvious neuronal apoptosis; (2) administration of IGF-1, the agonist of the PI3K-Akt pathway, increased the expression of pAkt remarkably and alleviated neuronal apoptosis significantly in rat hippocampi after experimental SAH; (3) Ly294002, the inhibitor of the PI3K-Akt pathway, decreased the expression of pAkt and aggravated neuronal apoptosis in the hippocampus after SAH. These findings indicate that the neuronal apoptosis in this model of experimental SAH in rats could be alleviated with the activation of the PI3K-Akt pathway and aggravated with its blockage. Hence, the PI3K-Akt pathway may play a crucial role in neuronal apoptosis after SAH, and its activation may reduce the severity of secondary brain injury following experimental SAH.

http://www.annclinlabsci.org/content/41/4/364.full

you can cross reference PI3K/AKT with cholestasis as well....

Peony(paeoniflorin is used in Chinese medicine for cholestasis....

Paeoniflorin ameliorates ANITinduced cholestasis by activating Nrf2 through an PI3K/Aktdependent pathway in rats : PTR

https://pubag.nal.usda.gov/pubag/article.xhtml?id=4569066&searchText=author%3 A"Jiabo+Wang"&searchField=

Really good post. I'm not a science wiz but what I take from this is that Accutane causes damage in this region of the brain.

Newer victims - pay attention to this, your depression isn't of the normal kind, it's a result of damage to the hippocampus.

Will antidepressants work??
only in the sense that they might take the edge off things but you will not get a cure from them until you repair damage!!

Thats the part we're all trying to work on.

15 hours ago, MonsterDiesel said:

Quote

Thus, topical use of a RAR antagonist as an antidote to block the cutaneous toxicity of Accutane should greatly improve patient compliance.

Quote

the topical use of RAR antagonist/inverse agonist as an antidote to block the cutaneous toxicities of Accutane should greatly improve patient compliance

It's a shame the whole text isn't visible - it would be interesting to know specifically what RAR antagonists are being referred to here.

18 hours ago, vdubz137 said:

Hi guys and gals,

I was only on Accutane for a little over a month. 40 mg per day. I noticed myself becoming super depressed, even more so than the slight symptoms of depression I had had in the past. I took myself off of it after my vision had started to become blurry. That was really troublesome. Now, 4 months after I have stopped, I have noticed my symptoms getting worse. My libido is almost gone. Even when I try to do it myself I notice that it's not the same as before. Orgasms are bland and I'm not as sensitive as I once was to stimuli. I'm single, but you know your own body enough to know how you used to be. I am extremely depressed, to the point of apathy. I don't enjoy things I used to enjoy before. To be happy or sad even I find that I have to make an effort to feel these feelings that came naturally before. I find my mind constantly foggy and confused at times. I find myself having trouble facing reality. I found myself googling my symptoms post Accutane which lead me to this blog. Has anyoneyou found any relief in their symptoms? I find these blogs helpful and comforting to know that I'm not alone. I fear I will never be the same person as I was before. Only a shadow of what I once was. There must be something in this world that can help me be me again.

welcome to the club.

9 hours ago, TrueJustice said:

Newer victims - pay attention to this, your depression isn't of the normal kind, it's a result of damage to the hippocampus.

Will antidepressants work??
only in the sense that they might take the edge off things but you will not get a cure from them until you repair damage!!

Thats the part we're all trying to work on.

That's why im considering trying NSI-189.  It's supposed to induce neurogenesis in the hippocampus but you know, im weary of buying yet another supplement specially since im unemployed

On 2/11/2017 at 0:36 AM, tryingtohelp2014 said:

Accutane = FOXO in the nucleus causing all of the epigenetic problems

Our goal is to get FOXO OUT of the nucleus.

you can do this by promoting IGF-1 or Insulin..... eat a tub of ice cream... shoot some hormones or peptides that promote IGF-1....  ONLY 3 minerals are capable of promoting PI3k/AKT they are copper, zinc or cadmium... with CU+2 being the most potent.     copper also has that inverse relationship with vitamin A in the liver.  it  raises the serum retinol, while lowering the liver esters.

These two pictures are almost scary....

I'd imagine this explains why mk-677 gives me acne?

1 hour ago, MonsterDiesel said:

That's why im considering trying NSI-189.  It's supposed to induce neurogenesis in the hippocampus but you know, im weary of buying yet another supplement specially since im unemployed

I liked NSI-189 but I didn't actually have lasting effects which I found strange. I only used it for a little over a month though because I've gotten 2 panic attacks towards the end of my time on it which I've never had panic attacks in my life and I really disliked that experience.

On 5/7/2011 at 11:07 AM, IndigoRush said:

Hello.

 

First of all, don't get too excited if you're in a similar situation to me and were hoping this post would hold the fix for long-term (Ro)accutane damage. I just wanted to express my situation and see if anyone can help.

 

I'm bored of reading depressing no-way-out answers and I refuse to give up and stop trying to fix myself. I'm also not inviting those who say the side effects aren't caused by this drug - I am 100% sure, and have read enough posts from others to know that Accutane isn't simply 'out' of your system after a month. I've read several theories into why things like IBS, Erectile Dysfunction and knee problems can occur months or years after stopping treatment. I'm talking about the liver storing the high-levels of Vitamin A, Accutane staying in the colon, and even something - which if it's true means only bad news - to do with DNA change and 'Telomere' shortening, which means a slow but sure decrease in health(This has been written by Nathan Carr, who you may of heard of).

But I'm not writing to find out which of these theories, if any, is true. I want to see if anyone can actually give good advice on supplements/diet, or whatever else, to repair damage from this poison.

Below, I will list the details of when I took this drug and what side effects I have + how I cope with life. One last thing - Anyone saying that these side effects are rare, i.e 1%, forget it. 1% reported. Since taking this drug, my life has been limited and difficult. I'm not in that 1% statistic because I haven't reported it directly to the manufacturer. I expect the figure is a lot higher.

 

As I said, side effects can come on AFTER taking this, so people could be ignorant to the cause. However, I know better, and after watching my health drop dramatically while/after taking Accutane, I can firmly say it's the cause. Let's begin ...

 

Basics: I'm 21 at the end of this month. It's now 5 years since I touched Ro-accutane (Ro-accutane is just the British name for it). I took it from December 2005 - May 2006. I was meant to finish in June, but stopped due to feeling very depressed/suicidal (because of the drug). My problems are below...

 

- Dry Eyes (Severe)

- E.D/ Low Libido (Started last year and has gone on consistently since)

- Hair-loss (Including eyebrows, facial hair 'gaps' and body hair)

- Slow Healing (Shaving is a pain now - No, it's not my technique)

- Lack of sebum (oil)

- Brain Fog/ Memory problems - Somewhat minor

- Anxiety (mainly because of the other side effects - i.e. dry eyes causing me to feel embarassed about eye contact)

- Excessive hair (Not related to head, but my beard grows high up on cheeks and even on the outside of my nose)

- I believe I look older than I should due to lack of oil

- Joint/Muscle problems - Aches/ Slow recovery

- Excessive sweating.. Terrible if I go running at the gym, for example.

- Dry mouth

- Nosebleeds more than I should

- Fatigue

- Overall depression and confusion (*Rhetorical question* Is this a direct symptom or am I like it because of all the other side-effects stressing me out?)

 

That's what I can think of for now. Of course, I wasn't told about half of these being a possibly problem and I was told any side-effects will be temporary. I was 15, so I had no reason not to trust the Doc's word.

 

I've tried lots of different supplements (a lot of which I still take just incase they are helping/slowing down the problems) including Omega 3, Biotin, B-Complex, Vitamin E, Vitamin D, Vitamin C, Collagen, Hyaluronic acid, Aloe Vera Juice, MSM, Colostrum, Garlic, Acetyl L-Carnitine, Acetyl L-Cysteine, Milk Thistle, Dandelion Root, Quercetin, Tumeric.

 

So, yeah, I've tried a lot of things. The Milk Thistle and Dandelion Root are recent additions because despite having my liver test results come back as positive, I've heard your liver can still not be functioning correctly and people are given liver tests monthly while taking this drug for a reason, right? I'm starting to eat better foods as this sh*t taught me that Natural is the way to go. I still binge on cakes and that occasionally - Mainly for comfort. I'm average weight and height, but want to cut out processed foods to support my body.

 

I don't want to make this EXTREMELY long, so I'll cut it short. I'm currently seeing a Homeopathy about these problems. And Yes, I know "Science says it's boll*cks", and I don't understand how it's supposed to work, but sometimes you have to think outside the box and give things a go. I don't have high hopes for things getting better these days, but I'm not giving up. There is so much more I could say, but let me know your thoughts. I don't want to hear negative and hopeless responses. What HAS helped you? Acne.org seems to be the biggest place to speak about this, but we NEED the word out, so the 'experts' can do the research instead of hoping for someone else to fix us.

 

Thanks for reading,

 

Indy.

https://www.google.com/amp/s/draxe.com/7-proven-chlorella-benefits-side-effects/amp/?client=safari

Since I read that isoretinoin was originally developed to be chemotherapy...recently saw this online..."Chlorellas high levels of chlorophyll have been shown to protect the body against ultraviolet radiation treatments while removing radioactive particles from the body." ...
"According to researchers from Virginia Commonwealth University Medical College,Cellular components and functions of the immune system remain at or near normal levels and are less adversely affected when patients are undergoing chemotherapy and/or taking immunosuppressive medications such as steroids."

worth looking into? I think so...

Hey,

I'm new here. Has anyone seen this? Seems interesting, but most of it is over my head...
The Effect of Different Doses of Isotretinoin on Pituitary Hormones: https://www.karger.com/Article/Pdf/375370

anyone had or known someone that has had a igfbp-3 blood test? Not sure if this could be capable of a abnormal result even if igf-1 blood test were normal. I believe they are both dependant on growth hormone

IGFBP-3 enters the cell nucleus by a mechanism that is incompletely understood, but involves its binding toimportin-.^[23]Within the nucleus, it can modulatenuclear hormone receptoractivity by direct binding toretinoid X receptor,retinoic acid receptor,^[24]vitamin D receptor,^[25]PPAR,^[26]andnur77,^[27]IGFBP-3 also interacts with DNA-dependent protein kinase within the nucleus to promote the repair of DNA damage.^[28]

1 hour ago, wheelinhealin said:

Hey,

I'm new here. Has anyone seen this? Seems interesting, but most of it is over my head...
The Effect of Different Doses of Isotretinoin on Pituitary Hormones: https://www.karger.com/Article/Pdf/375370

I believe alot of these hormone levels return to normal or at least in range after treatment. hatetane just posted a bunch of these test results that seemed to be pretty well in range. I've also had quite a few of these test(not all of them though) that came back well in range. Still a good panel of test to have checked though.

Sorry, is it Pituitary, Hippocampus or both that Roaccutane can damage??

I thought we were on hippocampus as a focus at the moment, not Pituitary. Sorry if I've missed something.

This is nothing related to hormones but I've been taking liver care supplements for the last month and I honestly do feel better.
cant say for sure so I will post again in another month.
I'm using himalaya liv 52 supplements honesty I do feel better

15 hours ago, vdubz137 said:

https://www.google.com/amp/s/draxe.com/7-proven-chlorella-benefits-side-effects/amp/?client=safari

Since I read that isoretinoin was originally developed to be chemotherapy...recently saw this online..."Chlorellas high levels of chlorophyll have been shown to protect the body against ultraviolet radiation treatments while removing radioactive particles from the body." ...
"According to researchers from Virginia Commonwealth University Medical College,Cellular components and functions of the immune system remain at or near normal levels and are less adversely affected when patients are undergoing chemotherapy and/or taking immunosuppressive medications such as steroids."

worth looking into? I think so...

what has chemotherapy to do with ultraviolet radiation treatments? I think this are two different things.

On 2/12/2017 at 1:55 AM, TrueJustice said:

Newer victims - pay attention to this, your depression isn't of the normal kind, it's a result of damage to the hippocampus.
Will antidepressants work??

The association between depression and hippocampal shrinkage has been known for many years now. Fortunately, this isn't very unique to Accutane:

"Such atrophy is centered in a brain region called the hippocampus. This structure plays a critical role in learning and memory, and the magnitude of the hippocampal volume loss (nearly 20% in some reports; refs. 24) helps explain some well-documented cognitive deficits that accompany major depression. . . . Moreover, more prolonged depressions were associated with more severe atrophy." - Source

If that is truly the mechanism in which Accutane causes cognitive problems and depression, it should be fairly treatable. Long-term administration of SSRIs is known to grow the hippocampus. In fact, when that ("brain growing") mechanism is blocked, the therapeutic effects of SSRIs are blocked as well. SSRIs obviously come with their own risks. NSI-189 is another option, but studies conducted on humans show that is grows the amygdala (part of brain associated with fear) to a greater extent than it grows the hippocampus, which may explain the panic attacks. Nevertheless, I found NSI-189 extremely helpful for recapturing emotional depth.

I was reading through government documents and FDA memos and found some fascinating information regarding vitamin A's effect on the brain. For those of us with anhedonia and depersonalization, I believe something far more sinister is going on:

That image sums up three troubling things: 1) Symptoms of acute vitamin A overdose mimic symptoms of schizophrenia, 2) Certain genes implicated in schizophrenia are involved in the retinoid signaling system. The retinoid receptor RXR is involved in the expression of dopamine neurons in the midregion of the brain, a part that is dysfunctional in schizophrenia patients. 3) Retinoic acid binds to the retinoid receptors RAR and RXR, which then eventually regulate the expression of genes pertaining to serotonin and dopamine.

It can be easy to dismiss that research because many of us are not experiencing hallucinations, but many of us have the negative symptoms of schizophrenia. We are unmotivated, feel disconnected from our surroundings, have cognitive dysfunctions, experience anhedonia, and have heavy brain fog. I believe it's possible Accutane uniquely messed up our retinoid receptors (at least for some of us). Although we may not have excess vitamin A in our bodies, signaling is still messed up. I know previous posts alluded to RARs and RXRs; hopefully this isn't redundant.

3 hours ago, brendan452 said:

This is nothing related to hormones but I've been taking liver care supplements for the last month and I honestly do feel better.
cant say for sure so I will post again in another month.
I'm using himalaya liv 52 supplements honesty I do feel better

Thanks for letting us now. Can you describe in more detail, what it means, to feel better? Is your skin less dry. Do you feel more energized or what is exactly the difference?

5 hours ago, Roland1968 said:

what has chemotherapy to do with ultraviolet radiation treatments? I think this are two different things.
 

In the article it states that, "Cellular components and functions of the immune system remain at or near normal levels and are less adversely affected when patients are undergoing chemotherapy and/or taking immunosuppressive medications such as steroids."

Retinoids are steroids and if you have taken Acccutane then you have essentially been on chemotherapy... I'm not sure what the effects of Chlorella would be after the fact, but if you click the link it seems like Chlorella (from a clean source) can repair damage done to the brain on a cellular level, due to these harsh drugs. It was an interesting article I wanted to share with the group. I only speak for myself but the all natural route could be the answer. That's not to say it isn't without risk but the less big pharma can shove down my throat the better