Acne.org Products
Sorry one more comment...slightly off topic I guess. I kind of squeaked my way into this thread. Hi I am Aaron btw.
I am aware this is likely a huge stretch, but if anyone waned to connect the dots... feel free. I've been off accutane for 2 years now. Several occasions over the past 2 years have resulted in large amounts of liquor being consumed.
In every occasion, the following morning has resulted in clear and hydrated skin... ( the red "scars" all over my temples would be 90% faded). The terrible dry irritated red disgusting skin would be no more. This would usually last for 1 day and then things would go back to normal. Is it too much of a stretch to say that the alcohol put some sort of stress on my liver that resulted in beautiful skin the next day? Or is probably blood sugar related? Oh god do I have diabetes? hehe.
Has anyone else noticed a vast improvement in their skin health the morning after drinking?
Thanks for any insights.
WE CAN DRINK IT OUT OF US! 
Reduced efficacy has been noted when isotretinoin is taken with heavy alcohol intake.66 Isotretinoin is metabolized by cytochrome P450 enzymes, these are inducible by ethanol and inhibited by some drugs
66. Soria C, Allegue F, Galiana J, Ledo A. Decreased isotretinoin efficacy during acute alcohol intake. Dermatologia. 1991;182:203.[PubMed]
Not sure if anyone here has heard of insulin, mTOR, and leptin being the main mechanism behind aging. I suggest people look into longevity research and how diet plays a major role. We always knew that calorie restricted animals lived longer and healthier lives but we didn't know the actual reason why until a few years ago. If we can lower each of these 3 pathways, it greatly upregulates our gene expression for maintenance and repair.
To keep insulin, mTOR, and leptin low: Basically eat 0 sugar (only fibrous carbs), moderate protein (lean body mass in kg x 0.8=roughly how much protein in grams we should eat a day; also, no more than 25g per meal from all sources), and the majority of cals from healthy fats (saturated, monounsaturated, and omega 3 polyunsaturated). This will enhance our ability to repair ourselves on a cellular level (DNA repair, autophagy, etc). It mimics starvation. You don't actually have to starve though to reap the same benefits as calorie restricted animals. Look up Nora Gedgaudas and Ron Rosedale for more info on the topic. Here is a very brief lecture on those ancient mechanisms.
They also talk about this in their books. This method of eating has the potential to drastically speed up our recovery and damage reversal.
Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity.
Isozymes of alcohol and other dehydrogenases convert ethanol and retinol to their corresponding aldehydes in vitro. In addition, new pathways of retinol metabolism have been described in hepatic microsomes that involve, in part, cytochrome P450s, which can also metabolize various drugs. In view of these overlapping metabolic pathways, it is not surprising that multiple interactions between retinol, ethanol, and other drugs occur. Accordingly, prolonged use of alcohol, drugs, or both, results not only in decreased dietary intake of retinoids and carotenoids, but also accelerates the breakdown of retinol through cross-induction of degradative enzymes. There is also competition between ethanol and retinoic acid precursors. Depletion ensues, with associated hepatic and extrahepatic pathology, including carcinogenesis and contribution to fetal defects. Correction of deficiency through vitamin A supplementation has been advocated. It is, however, complicated by the intrinsic hepatotoxicity of retinol, which is potentiated by concomitant alcohol consumption. By contrast, beta-carotene, a precursor of vitamin A, was considered innocuous until recently, when it was found to also interact with ethanol, which interferes with its conversion to retinol. Furthermore, the combination of beta-carotene with ethanol results in hepatotoxicity. Moreover, in smokers who also consume alcohol, beta-carotene supplementation promotes pulmonary cancer and, possibly, cardiovascular complications. Experimentally, beta-carotene toxicity was exacerbated when administered as part of beadlets. Thus ethanol, while promoting a deficiency of vitamin A also enhances its toxicity as well as that of beta-carotene. This narrowing of the therapeutic window for retinol and beta-carotene must be taken into account when formulating treatments aimed at correcting vitamin A deficiency, especially in drinking populations.
that then leads to this hypothesis:
"Accordingly, prolonged use of alcohol, drugs, or both, results not only in decreased dietary intake of retinoids and carotenoids but also accelerates the breakdown of retinol through cross-induction of degradative enzymes"
Is this why people might be getting a positive effect from weed and RSO vaping?! I think weed might be another cross inducer of the p450 enzyme, just like alcohol...bam, reduction in side effects (absolutely not a cure though...just another masking agent.) Though RSO is very high in Vitamin A and beta carotene, i dont quite understand that part yet.
So stay away from Vitamin A rich foods for a couple of days, get plastered, smoke weed, cross induce the p450 enzymes....temporarily draining the carotenoid/retinol levels and side effects.
Not sure if anyone here has heard of insulin, mTOR, and leptin being the main mechanism behind aging. I suggest people look into longevity research and how diet plays a major role. We always knew that calorie restricted animals lived longer and healthier lives but we didn't know the actual reason why until a few years ago. If we can lower each of these 3 pathways, it greatly upregulates our gene expression for maintenance and repair.
calorie restriction upregulates SIRT3 . all circles back to ROS and the mitochondria imo. its here that i think we'll find a cure.
http://journal.frontiersin.org/Journal/10.3389/fnagi.2013.00048/full
On 12/7/2014 at 5:25 PM, tryingtohelp2014 said:Some of us might have a BCDO2 polymorphism in the way we handle carotenoids /pre vitamin A. This could account for some of us not clearing accutane, and getting toxic side effects from eating normal vitamin A rich foods(we obviously didnt have this problem before accutane though!) It has been shown to induce ROS and a 9 fold increase in mnSOD !!! (another potential manganese link) Does mnSOD being generated at 9x the normal rate...drain manganese 9 times as fast?!Its also why you cant say for sure this drug gets excreted 100% the same way for everyone. We really have no idea!could our bodies be toxic in carotenoids and deficient in pro vitamin A at the same time??! (seeing how a lot of people come back deficient in Vitamin A and also have night blindness) Is this a defense mechanism by our body after accutane? does accutane epigenitically alter the BCDO2 gene expression?In BCDO2-deficient mice, carotenoid homeostasiswas abrogated, and carotenoids accumulatedin several tissues. In hepatic mitochondria, accumulatedcarotenoids induced key markers of mitochondrialdysfunction, such as manganese superoxide dismutase(9-fold), and reduced rates of ADP-dependentrespiration by 30%.Therefore, we speculatedthat carotenoid accumulation may interfere with mitochondrialfunction. To provide evidence for this hypothesis,we screened for expression of manganese superoxidedismutase (MnSOD), which is a reliable indicator ofmitochondrial stress and dysfunction (25). Immunoblotanalysis showed a 9-fold induction of MnSOD in hepaticmitochondria of carotenoid-supplemented BCDO2-defcient animals (Fig. 4E)[Edited link out] looks at the pictures... body just lit up with carotenoids...........Very funny, but this leads back to the previous poster who said when he gets drunk, the next day his skin feels normal. so i google alcohol and carotenoid depeletion and find this:Am J Clin Nutr. 1999 Jun;69(6):1071-85.Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity.
AbstractIsozymes of alcohol and other dehydrogenases convert ethanol and retinol to their corresponding aldehydes in vitro. In addition, new pathways of retinol metabolism have been described in hepatic microsomes that involve, in part, cytochrome P450s, which can also metabolize various drugs. In view of these overlapping metabolic pathways, it is not surprising that multiple interactions between retinol, ethanol, and other drugs occur. Accordingly, prolonged use of alcohol, drugs, or both, results not only in decreased dietary intake of retinoids and carotenoids, but also accelerates the breakdown of retinol through cross-induction of degradative enzymes. There is also competition between ethanol and retinoic acid precursors. Depletion ensues, with associated hepatic and extrahepatic pathology, including carcinogenesis and contribution to fetal defects. Correction of deficiency through vitamin A supplementation has been advocated. It is, however, complicated by the intrinsic hepatotoxicity of retinol, which is potentiated by concomitant alcohol consumption. By contrast, beta-carotene, a precursor of vitamin A, was considered innocuous until recently, when it was found to also interact with ethanol, which interferes with its conversion to retinol. Furthermore, the combination of beta-carotene with ethanol results in hepatotoxicity. Moreover, in smokers who also consume alcohol, beta-carotene supplementation promotes pulmonary cancer and, possibly, cardiovascular complications. Experimentally, beta-carotene toxicity was exacerbated when administered as part of beadlets. Thus ethanol, while promoting a deficiency of vitamin A also enhances its toxicity as well as that of beta-carotene. This narrowing of the therapeutic window for retinol and beta-carotene must be taken into account when formulating treatments aimed at correcting vitamin A deficiency, especially in drinking populations.
that then leads to this hypothesis:
"Accordingly, prolonged use of alcohol, drugs, or both, results not only in decreased dietary intake of retinoids and carotenoids but also accelerates the breakdown of retinol through cross-induction of degradative enzymes"
Is this why people might be getting a positive effect from weed and RSO vaping?! I think weed might be another cross inducer of the p450 enzyme, just like alcohol...bam, reduction in side effects (absolutely not a cure though...just another masking agent.) Though RSO is very high in Vitamin A and beta carotene, i dont quite understand that part yet.
So stay away from Vitamin A rich foods for a couple of days, get plastered, smoke weed, cross induce the p450 enzymes....temporarily draining the carotenoid/retinol levels and side effects.
Fantastic studies!! Very very interesting. My diet was EXTREMELY high in beta-carotene during and after accutane. Also, not sure I'd want to ingest alcohol to deplete my possibly built up carotenoids hah. So we should avoid carotenoids then? Also, wouldn't we have carotenodermia if we did have an overdose of them? And do you think we are deficient in true usable retinol? I don't get any strange symptoms when I ingest high amounts of beef liver (high in Vit A). I think I am going to continue eating vit A rich foods but stay away from the precursors to vit A.
Also here is a screenshot of an organic acids urine test I had done which measured some of the major metabolic pathway metabolites. The important ones all seemed okay. Not sure if me having built up carotenoids would result in mitochondrial dysfunction showing abnormal metabolites.. [Edited link out]
Another link to polymorphisms of the retinoic acid receptor alpha gene (RARA) associated with why certain people get the side effects and others do not. I am one of those who had nose bleeds AND arthralgia with myalgia. Also, my ALS did not increase during the accutane treatment. It actually went down.
http://www.ncbi.nlm.nih.gov/pubmed/23782583
On 12/7/2014 at 6:44 PM, tryingtohelp2014 said:calorie restriction upregulates SIRT3 . all circles back to ROS and the mitochondria imo. its here that i think we'll find a cure.
http://journal.frontiersin.org/Journal/10.3389/fnagi.2013.00048/full
"Remarkably, SIRT3 expression levels fluctuate with diet. Numerous studies have reported CR-induced increased SIRT3 expression (Palacios et al., 2009; Tauriainen et al., 2011). For example, mice on a 12-month CR diet exhibited increased SIRT3 levels in skeletal muscle compared to mice fed ad libitum (Palacios et al., 2009). In addition, Sirt3 mRNA expression was increased in liver, skeletal muscle, and adipose tissue of mice on a 30% CR diet (Tauriainen et al., 2011). By contrast, a chronic high fat diet (HFD) resulted in suppression of SIRT3 and elevated global mitochondrial protein acetylation (Hirschey et al., 2011). Akin to CR, exercise training in mice increased SIRT3 protein expression in cardiac and triceps muscles (Palacios et al., 2009)."
In terms of diet, is it only the caloric intake that determines whether or not it is upregulated? So a high fat diet will suppress SIRT3? Perhaps they restricted their calories from ALL sources (protein, fats, and carbs) equally. So the animal was in a caloric deficit (of course that'll enable repair mechanisms) that was brought back up to caloric maintenance/baseline when they upped the fat. I'm wondering what would've happened if they eliminated all sources of glucose and greatly diminished their protein intake while maintaining a high fat diet. Not sure if SIRT3 is blunted by intake of certain nutrients similar to the reproductive metabolic pathways of insulin, mTOR, and leptin. Do you plan on restricting overall total calories to achieve the effect? My plan right now is to eat according to my previous post.
-------
Do you guys have a greatly diminished cell turnover rate? My skin still does not heal at all even if I get the smallest little cut. I know Vit A helps rebuild tissues so perhaps we are deficient in it. And we are systemically messed up because our gut linings aren't recovering as fast as they should be. I know that I have all the antibodies to wheat proteins associated with celiac disease. I am known to have intestinal permeability brought on by accutane. Problem is: I've done everything to recover from it (and should be well by now) but can't seem to. I think it might be related to the delayed tissue healing. An endoscopy also revealed my stomach lining is extremely red and inflamed. I had H. pylori a year ago but now I've been tested multiple times (all negative). I still have chronic acid reflux with stomach pain.
EDIT: She mentions the sirtuins. Check it out:
EDIT2: CR study on monkeys. They got extreme benefits without even taking into account the now understood mechanisms behind aging.
http://www.primalbody-primalmind.com/primal-primates-live-longer/
EDIT3: Jack Kruse's site is a good resource for all things about longevity and regeneration/repair on a cellular level. He also gets quite technical for all the geeks out there 
[Edited link out]
Hi all,
On the advice of another member - moving my post here:
My name is Ben - 37 yr old male.
Never posted here before - as I thought for a long time that I was the only one suffering the ill affects of taking accutane.
Basically - about 15yrs ago I took a short course of accutane for what looking back was a really mild case of acne/oily skin.
When I was on it - had all the nasty effects as expected - dry skin, flushing etc. but seemed to clear up OK after finishing from memory.
Anyways - finished my 2 or 3 months or whatever it was - and as my pimples where coming back - my dermatologist proscribed another round of accutane.
This time I had some strange things going on with my skin - really dark circles under my eyes,skin becoming almost transparent-like and most alarming to me - facial capillaries coming up all over my cheek and nose. To cut to the chase - decided enough was enough and stopped taking any further accutane.
However to this day - 15yrs later - my skin has remained almost sort of like it is still on accutane.
It's very sensitive, flushes for whatever reason,have permanent broken capillaries over my cheeks and nose(my cheeks are permanently red),my skin looks so fragile it's almost transparent,very dark circles under my eyes,skin is really shiny and oily by the end of the day - but still feels dry,wrinkled and tight etc etc
I don't know how to describe it - but it's almost like the top layer of skin on my face is missing.
Has anyone had any luck repairing the skin on their face after accutane ie plumping,strengthening,repairing moisture levels?
Has anyone had any of the above side effects - skin thin and transparent,facial veins,permanent dryness?
Btw - my only skin care regimen consists of a cold shower once a day - and a light moisturiser.
It's hard to believe I took this sh*t 15yrs ago and it is still having such terrible effects on my skin.
Oh - for that magic time machine.
Thanks in advance.
Ben
On 12/9/2014 at 7:55 AM, UltraB said:Hi all,
On the advice of another member - moving my post here:
My name is Ben - 37 yr old male.
Never posted here before - as I thought for a long time that I was the only one suffering the ill affects of taking accutane.
Basically - about 15yrs ago I took a short course of accutane for what looking back was a really mild case of acne/oily skin.
When I was on it - had all the nasty effects as expected - dry skin, flushing etc. but seemed to clear up OK after finishing from memory.
Anyways - finished my 2 or 3 months or whatever it was - and as my pimples where coming back - my dermatologist proscribed another round of accutane.
This time I had some strange things going on with my skin - really dark circles under my eyes,skin becoming almost transparent-like and most alarming to me - facial capillaries coming up all over my cheek and nose. To cut to the chase - decided enough was enough and stopped taking any further accutane.
However to this day - 15yrs later - my skin has remained almost sort of like it is still on accutane.
It's very sensitive, flushes for whatever reason,have permanent broken capillaries over my cheeks and nose(my cheeks are permanently red),my skin looks so fragile it's almost transparent,very dark circles under my eyes,skin is really shiny and oily by the end of the day - but still feels dry,wrinkled and tight etc etc
I don't know how to describe it - but it's almost like the top layer of skin on my face is missing.
Has anyone had any luck repairing the skin on their face after accutane ie plumping,strengthening,repairing moisture levels?
Has anyone had any of the above side effects - skin thin and transparent,facial veins,permanent dryness?
Btw - my only skin care regimen consists of a cold shower once a day - and a light moisturiser.
It's hard to believe I took this sh*t 15yrs ago and it is still having such terrible effects on my skin.
Oh - for that magic time machine.
Thanks in advance.
Ben
After reading your post....you have a Collagen deficiency/defect 100% guaranteed. The more i think about it, the more i think all of our long term symptoms resemble a collagen defect.
Once again, points to manganese, Vitamin C, zinc. If you look at what accutane upregulates epigenetically... there are a lot of collagen genes that are affected. [Edited link out[
[Edited link out] page 5-6 mentions Mn Zn C
here is a list of symptoms from that article(page 13) that almost describes exactly what you wrote.:
A new discovery has been made in finding out what actually causes hair loss, namely: the hardening of collagen. Persons who do not suffer from hair loss have supple collagen and persons who begin showing signs of hair loss have hardened collagen. Collagen hardening interferes with the healthy functioning of the hair roots. The vital exchange process of the hair follicle cycle is disrupted and the hair becomes suffocated.
Collagen is the main protein of connective tissue in animals and the most abundant protein in mammals,[1] making up about 25% to 35% of the whole-body protein content. In muscle tissue it serves as a major component of endomysium. Collagen constitutes 1% to 2% of muscle tissue, and accounts for 6% of the weight of strong, tendinous muscles.[2] The gelatin used in food and industry is derived from the partial hydrolysis of collagen.
http://www.thewestminsterpractice.com/blog/hair-loss-is-collagen-the-answer/
Also, is anyone here experiencing barely visible half moons under the nails. The white part. It is barely visible and from what I read it has to do with connective tissue.
Sorry one more comment...slightly off topic I guess. I kind of squeaked my way into this thread. Hi I am Aaron btw.
I am aware this is likely a huge stretch, but if anyone waned to connect the dots... feel free. I've been off accutane for 2 years now. Several occasions over the past 2 years have resulted in large amounts of liquor being consumed.
In every occasion, the following morning has resulted in clear and hydrated skin... ( the red "scars" all over my temples would be 90% faded). The terrible dry irritated red disgusting skin would be no more. This would usually last for 1 day and then things would go back to normal. Is it too much of a stretch to say that the alcohol put some sort of stress on my liver that resulted in beautiful skin the next day? Or is probably blood sugar related? Oh god do I have diabetes? hehe.
Has anyone else noticed a vast improvement in their skin health the morning after drinking?
Thanks for any insights.
Interesting, some posters on here have said alcohol should avoided and makes symptoms worse...usually that was sexual symptoms though. Do you find everytime you drink your skin is better? Does it improve even more over time?
On 12/10/2014 at 12:42 AM, shadeo14 said:Interesting, some posters on here have said alcohol should avoided and makes symptoms worse...usually that was sexual symptoms though. Do you find everytime you drink your skin is better? Does it improve even more over time?
Every time I drink a significant amount of alcohol. =D . You could say I tend to drink too much on occasions. But yes, every time I drink a "significant amount" my skin makes a 90% improvement, its weird. I usually drink hard alcohol if that is relevant. I have never had any ED issues following my accutane.
I don't think the "hungover effect" increasingly improves my skin though. The skin the following morning is the same each time, but great.
I am incredibly temped to start on maganese supplements. It seems I have all of the symptoms tryingtohelp keeps pointing out along with hair thinning and just terrible hair in general.
On 12/9/2014 at 7:55 AM, UltraB said:Hi all,
On the advice of another member - moving my post here:
My name is Ben - 37 yr old male.
Never posted here before - as I thought for a long time that I was the only one suffering the ill affects of taking accutane.
Basically - about 15yrs ago I took a short course of accutane for what looking back was a really mild case of acne/oily skin.
When I was on it - had all the nasty effects as expected - dry skin, flushing etc. but seemed to clear up OK after finishing from memory.
Anyways - finished my 2 or 3 months or whatever it was - and as my pimples where coming back - my dermatologist proscribed another round of accutane.
This time I had some strange things going on with my skin - really dark circles under my eyes,skin becoming almost transparent-like and most alarming to me - facial capillaries coming up all over my cheek and nose. To cut to the chase - decided enough was enough and stopped taking any further accutane.
However to this day - 15yrs later - my skin has remained almost sort of like it is still on accutane.
It's very sensitive, flushes for whatever reason,have permanent broken capillaries over my cheeks and nose(my cheeks are permanently red),my skin looks so fragile it's almost transparent,very dark circles under my eyes,skin is really shiny and oily by the end of the day - but still feels dry,wrinkled and tight etc etc
I don't know how to describe it - but it's almost like the top layer of skin on my face is missing.
Has anyone had any luck repairing the skin on their face after accutane ie plumping,strengthening,repairing moisture levels?
Has anyone had any of the above side effects - skin thin and transparent,facial veins,permanent dryness?
Btw - my only skin care regimen consists of a cold shower once a day - and a light moisturiser.
It's hard to believe I took this sh*t 15yrs ago and it is still having such terrible effects on my skin.
Oh - for that magic time machine.
Thanks in advance.
Ben
I share all of these symptoms man, along with thinning, dry and brittle hair. I appreciate the struggle.
On the one cheek it seems like damaged dark red blood vessels are showing among a sea of persistent redness. The bags underneath my eyes are so bad especially for my age at 21. Also wanted to point out "but its almost like the top layer of my face is missing". I feel this as well. And funny enough when I think about it...a night after heavy drinking it seems as if I have slightly thicker, healthier skin all over my face.
How is your hair if you don't mind me asking? . Have you noticed that reducing showering and water touching your face greatly improves/dulls the redness on your face?
On 12/9/2014 at 12:41 PM, tryingtohelp2014 said:After reading your post....you have a Collagen deficiency/defect 100% guaranteed. The more i think about it, the more i think all of our long term symptoms resemble a collagen defect.
Once again, points to manganese, Vitamin C, zinc. If you look at what accutane upregulates epigenetically... there are a lot of collagen genes that are affected.[Edited link out]
[Edited link out] page 5-6 mentions Mn Zn C
here is a list of symptoms from that article(page 13) that almost describes exactly what you wrote.:
Tendency to blush or flush easilyPersistent facial rednessSmall visible blood vesselsBumps and pus-filled pimples on the face(inflammatory papules and pustules)Facial discomfort”burning or stingingsensation, tightness, dryness or itchBurning, itching, or watery eyes and/orswollen eyelidsIt is predominantly found in fibrous tissuessuch as fascia, ligaments, tendons and skin.However, it is also found in abundance in ourcartilage, bones, cornea's, intervertebraldiscs, our gut and our blood vesselsManganese plays a role in collagen development. A person with a manganese deficiency may have difficulty healing abrasions and cuts. Manganese deficiency may inhibit the proper amount of collagen created in the body. - See more at: [Edited link out]
I'm trying to refrain from sounding incredibly optimistic (it has failed me in the past) but I think you nailed my suffering cause (even though you weren't even replying to me 
) .
I investigated collagen deficiency a little more, I also suffer from hunchback, and dry splitting hairs along with ALL of the symptoms listed. I'm a guy so I can get by with short hair, but it starts to split after about 2.5 inches on the sides of my head 
.
Looking on my past of goggle diagnosing, I have tried zinc and vitamin C supplements on their own for significant times, so i'm guessing something is blocking my ability to receive these vitamins. I guess I potentially have a manganese deficiency? Is there anything that would work great with the manganese deficiency?
Sorry to hear you are suffering the same sh*t.
My hair has definitely thinned and started to recede - dunno what the solution is there.
Do you get red eyes too?
The dark circles under my eyes are caused by lots of little blood vessels that seem permanently inflamed - have you had any luck reducing these?
Have you tried anything for the broken capillaries?
I tried diathermy(electrocoagulation) as I was too scared of laser - it either had no effect or made them worse.
Do you find if you use too much moisturiser - that it just sits on the skin like a shiny slick? Almost like my skin can't absorb it.
I find my skin looks best when I don't think about it - don't stress an get a good sleep.
Apart from that - nothing else seems to work for my skin.
Good luck my friend.
Cheers.
Ben
On 12/10/2014 at 6:38 AM, Kokodu said:Should I worry about DHEA or it is acceptable level?
Chart of hormonal pathways: [Edited link out]
I would not worry about a high DHEA. If it is low, then I'd be worried.
As for everyone thinking they have a collagen deficiency, I think it is possible but unlikely. I do know that I am deficient in Vitamin A, biotin, and Vitamin C despite supplementation: all majorly involved in skin health. Upon further review of this article [Edited link out] and the studies included about accutane, I have come to the conclusion that us accutane sufferers are indeed deficient in Vitamin A. (The major root cause of most of our symptoms imo). Vitamin A is greatly needed for eye health (night vision and eye floaters/light sensitivity anyone?), immune function (gut infections anyone?), bone remodeling (joint pain anyone?), skin health (poor skin rejuvenation/extremely thin skin anyone?), formation of blood cells, shields fats from being oxidized.. It affects cell growth and differentiation.. so yeah.. all major body functions.
I am planning on greatly increasing my Vitamin A in my diet to see how it affects me. I do know that I am doing slightly better in the past few months since I've been eating a pound of grass fed beef liver each week (high in preformed Vit A).
My plan is to greatly up my preformed Vit A content from animal sources and to increase certain nutrients to aid in utilizing the Vit A. Zinc helps create retinol-binding proteins that transfer it around the body. Also, iron deficiency can affect Vit A metabolism. Check your ferritin levels. I would make sure it is above 100 ng/ml. When taking high doses of Vitamin A, be sure it is in balance with Vitamin D and K2. Good video explaining the mechanisms behind that:
Also, Vitamin A prevents excessive uncarboxylated K2 dependent proteins from being produced (to protect in soft tissue calcification; not that that's our main concern hah).
The way I am going to increase my Vit A in my diet is through loads of beef liver and a blend of high vitamin butter and cod liver oil. The brand I am going to use is the gel form of Blue Ice Royal Butter Oil/Fermented Cod Liver Oil Blend - Non-Flavored by Green Pasture. It is about $70 and an entire 240ml bottle contains about 456,000IU vit A and 93,600 vit D. I am going to use about a teaspoon a day (9500IU vit A, 1950IU vit D. Wish I could locate some polar bear liver haha. Also going to be doing some detoxing through liver flushing, kidney cleanses, colonics, colemas, and enemas. Should be great fun
Research into 13-cis-retinoic acid (13CRA which is isotretinoin) metabolism and how it differs from normal Vit A. Also, Vitamin A stores in the liver so we may have a bunch of the accutane's 13CRA built up in us. Some people report bad symptoms when they eat Vit A. This may be due to the synthetic 13CRA being released finally and replaced with the natural Vit A.
Also, it isn't the 13CRA (isotretinoin) that directly screws up our DNA. 13CRA can't bind to cellular retinoid-binding proteins (CRABP), which are the proteins that transmit the poison into our nucleus to activate nuclear retinoid receptors (RAR) which then bind to the DNA to initiate transactivation of retinoid-responsive elements. It is the all-trans-retinoic acid (ATRA) that can bind to the transporter proteins. However, 13CRA greatly converts to ATRA then the ATRA goes on to damage our DNA.
In a study on rats they treated 2 groups, one with ATRA and one with 13CRA (Isotretinoin).
The ones treated directly with the 13CRA had higher plasma concentrations of ATRA than the ATRA treated group. This shows that 13CRA results in greater DNA damage. 13CRA is highly teratogenic. http://toxsci.oxfordjournals.org/content/63/1/82.full
If someone wants to critique what I said, please do. I am just thinking out loud.
Should I worry about DHEA or it is acceptable level?
Lots of Stuff
I had 2 teapsoons of the cod liver oil brand you mentioned daily for 2 months. I noticed no effect .
I also agree that a lot of our symptoms line up with a vitamin a deficiency, but I never seem to improve when supplementing vitamin A. I read earlier that our body might be tricking ourselves into thinking we have vitamin A when we really are deficient of it = / .
I truly believe the accutane never left our systems. There has to be some way to flush it out. I am seeing a doctor next week, im going to entertain the idea of a liver flush and ask her for some tests to see if I am deficient in anything.
I also tried juice fasting for 2 days, but my lifestyle just didn't allow me to continue. My body entered ketosis in 16 hours in to the fast. I'm pretty sure it wasn't finished detoxing so I am tempted to try that again. Please tell me how the liver flush goes!
Why do you think a collagen deficiency is unlikely? just curious.
Sorry to hear you are suffering the same sh*t.
My hair has definitely thinned and started to recede - dunno what the solution is there.
Do you get red eyes too?
The dark circles under my eyes are caused by lots of little blood vessels that seem permanently inflamed - have you had any luck reducing these?
Have you tried anything for the broken capillaries?
I tried diathermy(electrocoagulation) as I was too scared of laser - it either had no effect or made them worse.
Do you find if you use too much moisturiser - that it just sits on the skin like a shiny slick? Almost like my skin can't absorb it.
I find my skin looks best when I don't think about it - don't stress an get a good sleep.
Apart from that - nothing else seems to work for my skin.
Good luck my friend.
Cheers.
Ben
Hey Ben, my eyes have been for the most part healthy and unaffected (or at least I think so). For the broken capillaries , my previous doctor thought it was rosascea or eczema. For me specifically, I think its some sort of accutane induced eczema (i had cases as a child) for the redness, but then again i have no idea. I tried hydrocortizone cream but had no luck.
For moisturizer, I think my skin actually absorbs it =/ . I stay away from all products on my face as EVERYTHING seems to irritate it.
Why do you think a collagen deficiency is unlikely? just curious.
I mean it is possible but it's not like it's the cause of our health problems. Why would accutane deplete our collagen? Plus, I eat a lot of bone broth daily which is loaded with all the different matrix material (including collagen) and I still have all the symptoms.
I don't think the 2 teaspoons of the cod liver oil was enough vit A. Did you also eat liver with it? We should probably be getting over 50,000IU vit A/day.
Also, I have been eating an incredibly nutrient rich diet loaded with different supplements over the past year and I still have a whole bunch of nutrient deficiencies (especially ones that I've been supplementing heavily with). I'm pretty sure our guts are just absolutely destroyed from the lack of regeneration that would normally take place. We need to correct the vitamin A deficiency somehow which should return our cell turnover rate back to normal. And we need to do whatever possible to get the synthetic vit A out of our systems. I just bought a colema board which allows me to do great colon cleanses whenever I want from home. It is almost as good as professional colon hydrotherapy. I will keep everyone updated with my progress on how these detoxes affect my symptoms.
Edit: I also think that a lot of us picked up gut infections during the course of accutane due to vit A deficiency. That is another possible reason why some people experience symptoms long after the course and others do not. Some people get lucky and do not pick up an infection. I know that I got an overgrowth of bacteria and H. pylori. Going to be getting a breath test soon for SIBO. Will update with results..
Why do you think a collagen deficiency is unlikely? just curious.
I mean it is possible but it's not like it's the cause of our health problems. Why would accutane deplete our collagen? Plus, I eat a lot of bone broth daily which is loaded with all the different matrix material (including collagen) and I still have all the symptoms.
ARGHHHHHHHH!
DO NOT TAKE COD LIVER OIL!
accutane depletes our collagen cofactors because of upregulation while on the drug. What Ben described is a collagen problem, no if ands or buts.
accutane causes oxidative damage (ROS) ----> mnSOD is used up at 9x the normal levels. ---> manganese is the cofactor for mnSOD and is depleted. ---->manganese is also a main the cofactor for collagen, thats why its put in all of the joint pain formulas.
mnSOD detoxifies us at the cellular level. you cant go deeper than this.
Looking on my past of goggle diagnosing, I have tried zinc and vitamin C supplements on their own for significant times, so i'm guessing something is blocking my ability to receive these vitamins. I guess I potentially have a manganese deficiency? Is there anything that would work great with the manganese deficiency?
I too have taken zinc for extended periods years ago. i fear i may have made things worse. taking zinc and vitamin C by themselves, only further depletes manganese.
As for everyone thinking they have a collagen deficiency, I think it is possible but unlikely. I do know that I am deficient in Vitamin A, biotin, and Vitamin C despite supplementation:
you do read what im typing right? even this post SCREAMS at me. you can supplement all the vitamin C and biotin you want, but if it cant be utilized, its useless... what is needed for biotin and vitamin C utilization?
Mn Deficiency Symptoms
Ineffective utilization of several key nutrients Choline (see below), thiamin, ascorbic acid, and biotin all require adequate manganese to be utilized by the body.
As for everyone thinking they have a collagen deficiency, I think it is possible but unlikely. I do know that I am deficient in Vitamin A, biotin, and Vitamin C despite supplementation:
you do read what im typing right? even this post SCREAMS at me. you can supplement all the vitamin C and biotin you want, but if it cant be utilized, its useless... what is needed for biotin and vitamin C utilization?
Mn Deficiency Symptoms
Ineffective utilization of several key nutrients Choline (see below), thiamin, ascorbic acid, and biotin all require adequate manganese to be utilized by the body.
Why should we avoid the cod liver oil?
As for everyone thinking they have a collagen deficiency, I think it is possible but unlikely. I do know that I am deficient in Vitamin A, biotin, and Vitamin C despite supplementation:
you do read what im typing right? even this post SCREAMS at me. you can supplement all the vitamin C and biotin you want, but if it cant be utilized, its useless... what is needed for biotin and vitamin C utilization?
Mn Deficiency Symptoms
Ineffective utilization of several key nutrients Choline (see below), thiamin, ascorbic acid, and biotin all require adequate manganese to be utilized by the body.
I enjoyed this read.
I drew some more personal parallels:
Childhood Asthma: intensive care right after birth and struggled badly with asthma for most of my child hood. I have outgrown it for the most part, but something to note I guess.
Iron Overload: Both my cousin and grandpa have hemachromatosis (Too much iron being produced in the blood) I am getting some bloodwork done next week. This disease is hereditary.
And just because... but probably not relevant at all: Alcohol and Manganese levels: http://www.traceelements.com/Docs/The%20Nutritional%20Relationships%20of%20Manganese.pdf
" Alcohol increases the hepatic manganese level and apparently doubles its absorption.6"
Thinking about this some more.....there are two ways Manganese is potentially depleted by accutane...
1. Fighting ROS induced by accutane by way of mnSOD
2. In the initial glucurodination of accutane from the body
Follow me here......
http://en.wikipedia.org/wiki/Glucuronosyltransferase
Glucuronosyltransferases are responsible for the process of glucuronidation, a major part of phase II metabolism. Arguably the most important of the Phase II (conjugative) enzymes, UGTs have been the subject of increasing scientific inquiry since the mid-to-late 1990s.
The reaction catalyzed by the UGT enzyme involves the addition of a glucuronic acid moiety to xenobiotics and is the most important pathway for the human body's elimination of the top 200 drugs. It is also the major pathway for foreign chemical (dietary, environmental, pharmaceutical) removal for most drugs, dietary substances, toxins and endogenous substances.
http://www.jbc.org/content/278/34/32219.full
glucuronosyltransferase = (GlcAT-I)
"Analysis of the results clearly showed that GlcAT-I requires the metal for activity and that the velocity of the enzyme was remarkably stimulated by Mn2+"
(now im excited)
"Here, we showed that the activity of GlcAT-I was strictly dependent on the presence of divalent ions. Activity was undetectable in the absence of metal cations, thus emphasizing the obligatory presence of these cofactors for the function of the enzyme. Among all the cations tested with various sizes and van der Waals volumes, Mn2+ exhibited the highest apparent Vmax. Compared with Mn2+, Mg2+ and Zn2+ resulted in a 2-fold lower effect, whereas Ca2+ and Ba2+ ions did not activate the enzyme. This result points out an optimal interaction of Mn2+ with the GlcAT-I protein. "
What this shows is the catalyst for glucurodination (glucuronosyltransferase),is most affected by the presence of manganese!? It also shows that if you are deficient, the enzyme shuts off. If accutane is removed from the body by glucurodination, and the body gets overwhelmed in trying to detoxify this stuff and cant...does it get stored?! Does this account for side effects 15-20 years later?
HOLY #%$$ !!
Glucuronidation of toxic substances[edit]
In the animal body, glucuronic acid is often linked to the xenobiotic metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids,glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds, and this linkage process is known as glucuronidation.[2]Glucuronidation occurs mainly in the liver, although the enzyme responsible for its catalysis, UDP-glucuronyltransferase, has been found in all major body organs, e.g.,intestine, kidneys, brain, adrenal gland, spleen, and thymus.[3][4]
The substances resulting from glucuronidation are known as glucuronides (or glucuronosides) and are typically much more water-soluble than the non-glucuronic acid-containing substance from which they were originally synthesised. The human body uses glucuronidation to make a large variety of substances more water-soluble, and, in this way, allow for their subsequent elimination from the body through urine or faeces (via bile from the liver). Hormones may also be glucuronidated to allow for easier transport around the body. Pharmacologists have linked drugs to glucuronic acid to allow for more effective delivery of a broad range of substances. Sometimes toxic substances are also less toxic after glucuronidation.
The conjugation of xenobiotic molecules with hydrophilic molecular species such as glucuronic acid is known as phase II metabolis
Leaky gut, red and inflamed stomach lining you say....
[Edited link out]
On 12/10/2014 at 9:05 PM, tryingtohelp2014 said:Thinking about this some more.....there are two ways Manganese is potentially depleted by accutane...
1. Fighting ROS induced by accutane by way of mnSOD
2. In the initial glucurodination of accutane from the body
Follow me here......
http://en.wikipedia.org/wiki/Glucuronosyltransferase
Main article: GlucuronidationGlucuronosyltransferases are responsible for the process of glucuronidation, a major part of phase II metabolism. Arguably the most important of the Phase II (conjugative) enzymes, UGTs have been the subject of increasing scientific inquiry since the mid-to-late 1990s.
The reaction catalyzed by the UGT enzyme involves the addition of a glucuronic acid moiety to xenobiotics and is the most important pathway for the human body's elimination of the top 200 drugs. It is also the major pathway for foreign chemical (dietary, environmental, pharmaceutical) removal for most drugs, dietary substances, toxins and endogenous substances.
http://www.jbc.org/content/278/34/32219.full
glucuronosyltransferase = (GlcAT-I)
"Analysis of the results clearly showed that GlcAT-I requires the metal for activity and that the velocity of the enzyme was remarkably stimulated by Mn2+"
(now im excited)
"Here, we showed that the activity of GlcAT-I was strictly dependent on the presence of divalent ions. Activity was undetectable in the absence of metal cations, thus emphasizing the obligatory presence of these cofactors for the function of the enzyme. Among all the cations tested with various sizes and van der Waals volumes, Mn2+ exhibited the highest apparent Vmax. Compared with Mn2+, Mg2+ and Zn2+ resulted in a 2-fold lower effect, whereas Ca2+ and Ba2+ ions did not activate the enzyme. This result points out an optimal interaction of Mn2+ with the GlcAT-I protein. "
What this shows is the catalyst for glucurodination (glucuronosyltransferase),is most affected by the presence of manganese!? It also shows that if you are deficient, the enzyme shuts off. If accutane is removed from the body by glucurodination, and the body gets overwhelmed in trying to detoxify this stuff and cant...does it get stored?! Does this account for side effects 15-20 years later?
HOLY #%$$ !!
Glucuronidation of toxic substances[edit]
Main article: GlucuronidationIn the animal body, glucuronic acid is often linked to the xenobiotic metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids,glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds, and this linkage process is known as glucuronidation.[2]Glucuronidation occurs mainly in the liver, although the enzyme responsible for its catalysis, UDP-glucuronyltransferase, has been found in all major body organs, e.g.,intestine, kidneys, brain, adrenal gland, spleen, and thymus.[3][4]
The substances resulting from glucuronidation are known as glucuronides (or glucuronosides) and are typically much more water-soluble than the non-glucuronic acid-containing substance from which they were originally synthesised. The human body uses glucuronidation to make a large variety of substances more water-soluble, and, in this way, allow for their subsequent elimination from the body through urine or faeces (via bile from the liver). Hormones may also be glucuronidated to allow for easier transport around the body. Pharmacologists have linked drugs to glucuronic acid to allow for more effective delivery of a broad range of substances. Sometimes toxic substances are also less toxic after glucuronidation.
The conjugation of xenobiotic molecules with hydrophilic molecular species such as glucuronic acid is known as phase II metabolis
Leaky gut, red and inflamed stomach lining you say....
[Edited link out]
Very very great work! I am in complete agreement with you about the ways accutane could deplete manganese and the following problems that stem from that like decreased collagen production.
However, I had a micronutrient test done (spectracell labs) 1 year and 2 months post accutane when my health was at its worst (before I changed my diet away from the SAD). Here is what the results showed:
Patient Results (% Control) Reference Range (greater than)
DEFICIENCIES
Folate 31 >32%
Vitamin A (Retinol) 68 >70%
Coenzyme Q-10 86 >86%
Alpha Lipoic Acid 81 >81
BORDERLINE DEFICIENCIES
B3 Niacinamide 83 >80%
B5 Pantothenate 10 >07%
B6 Pyridoxine 58 >54%
B7 Biotin 38 >34%
Inositol 62 >58%
Vitamin D3 (Cholecalciferol) 54 >50%
Antioxidant Function 45 >40%
-----
Manganese 64 >50%
Not sure how accurate the test is but according to the results, I wasn't deficient in manganese. Unsure of any better tests to more accurately assess a true deficiency. I am going to be taking a manganese supplement soon but I won't go crazy with it. I'll probably take in like 10-15g every 2-3 days on an empty stomach. Mark Sisson says common deficiency symptoms include: asthma, low T4, low HDL, and poor utilization of certain key nutrients like vit C and biotin. I don't have asthma. My Total T4 and Free T4 are both in normal range. My HDL is 70mg/dl, so it's quite good. I do have the ascorbic acid and biotin deficiency despite supplementation however (as indicated by an organic acids urine test). It's possible that I am just not absorbing the nutrients due to my high probability of having Celiac (I have all the antibodies for it). Also, I'm not sure if lack of utilization shows up as deficiency.
Couple forum posts that seem to think that mnSOD could be inhibited due to other factors besides manganese deficiency. Perhaps we could have something else going on that is preventing our healing. Just throwing more ideas out.
"The observation that the gene for Mn-SOD is partially blocked is a very big concern. Something is blocking it, something important to your health. Without knowing what that is you are in the dark. It only might be manganese. Personally I think its probably cytokines or related hormones, but this is only opinion - the science is not advanced enough for anyone to be sure."
"I had a low SODase and took mineral supplements and they did not help that much. What did help was getting rid of my nickel DNA adducts. JMH reckoned that my nickel DNA adducts were affecting the gene for the Mn SODase in me. Once I did a nickel chelation with l-methionine and got rid of my nickel DNA adducts my SODase shot up well into normal levels.
I don't know what other things can affect the gene for Mn SODase."
"Partial blocking of the Mn-SOD gene means that your cells will not be able to make enough of the manganese superoxide dismutase enzyme. This enzyme is needed by the mitochondria to convert superoxide (oxidizing free radicals that are generated in the normal metabolism of the mitochondria) into hydrogen peroxide. The hydrogen peroxide is then normally dealt with by glutathione, together with the glutathione peroxidase enzyme, and is converted into water. Without enough Mn-SOD, your cells will suffer from oxidative stress.
Some of the genes in ME/CFS are blocked by what are called DNA adducts. These are things that bind to the DNA (which form the genes), and which do not belong there. The DNA adducts prevent the genes from being expressed properly. That means that their genetic code is not translated into producing the proteins that they code for, and in your case, one of these proteins is the Mn-SOD enzyme.
The DNA adducts are toxins. Nickel is one that has been found in many cases. There are also several others that show up a lot, including a chemical used in permanent hair dyes.
In my hypothesis, the reason for the presence of these toxins, acting as DNA adducts, is that glutathione depletion has caused the normal detoxication system in the body to become dysfunctional. As a result, toxins that are normally taken out routinely are now allowed to build up, and they "gum up the works" so to speak. The methylation treatments are designed to restore normal glutathione levels, among other benefits. More information is available at www.cfsresearch.org by clicking on CFS/M.E. and then on my name."
http://forums.phoenixrising.me/index.php?threads/sodase-test-result-manganese-deficiency-help.7686/
I do happen to have permanent nickel titanium retainers on both my upper and lower sets of teeth. That combined with constant stomach acid erosion could be a potential cause of concern for me. Not sure.. I am getting my retainers taken out next Monday regardless.
tryingtohelp2014: do you think we have vitamin A deficiency? Why do you say we shouldn't be taking in cod liver oil? Or do you just think that is not the main issue? I really appreciate all your research into MnSOD and free radical damage due to ROS. You're doing all of us a great service. I feel like we are making great progress in understanding some of the mechanisms behind this drug
Do you think we're all just dehydrated, it makes the most sense. Yesterday I was doing blood work and the lady said she couldn'tfind any veins because I was "severely dehydrated". That could explain the ed because of blood flow but I don't think I would have lowered libido because of that. The sad truth is that if I didn't have any sexual problems I would still be taking this damn drug. And about the alcohol I like that idea for the skin but I have sexual side effects as well. I also read that you lose manganese through excessive sweating which I had while on the drug. So I probably got rid of all the good and bad toxins
Is taking finasteride profitable for us, assuming accutane has caused our hairloss? I have low DHT, so I guess the problem is that my hair follicles are too sensitive. I've been taking finasteride for couple months and it has just reduced my hair loss little bit.
I dont want to scare you but have you heard of PFS. www.propeciahelp.com