Jemini,
Thanks for clearing that up for me.
Actually, I am into lifting weights, and I see alot of guys who juice with clear skin. It makes sense though, that stimulating any kind of hormones may aggravate acne.I don't have any known "sensitivities" to stress though. I think I will experiment with it.
Well no, you're not megadosing on Accutane, but I've read that its like megadosing on Vitamin A. A theory is that some people have an overactive enzyme that breaks down retinoic acid before it can be used. So basically you're flooding youre body with Vitamin fast enough that not all of it gets broken down to be used.
I still would like to hear you're opinion though, on the fluxing of hormones though! If you don't mind.
It's interesting that you talk about thyroid receptors. My mom has hypthyroidism. I mentioned earlier that, I take after my dad in more ways than one though.
Glad to hear you're thoughts Jemini.
Not sure if this has been mentioned already, but in the same vain as flax lignans and sesamin, it is purported that Resveratrol too may be estrogenic:
'While the health benefits of resveratrol seem promising, one study has theorized that it may stimulate the growth of human breast cancer cells, possibly because of resveratrol's chemical structure, which is similar to a phytoestrogen.[62] [63] However, other studies have found that resveratrol actually fights breast cancer.[64][65] Citing the evidence that resveratrol is estrogenic, some retailers of resveratrol advise that the compound may interfere with oral contraceptives and that women who are pregnant or intending to become pregnant should not use the product, while others advise that resveratrol should not be taken by children or young adults under 18, as no studies have shown how it effects their natural development."[66]'
From wiki
Well no, you're not megadosing on Accutane, but I've read that its like megadosing on Vitamin A. A theory is that some people have an overactive enzyme that breaks down retinoic acid before it can be used. So basically you're flooding youre body with Vitamin fast enough that not all of it gets broken down to be used.
Jemini,
Haha, damn, do you have a degree in this field of something?! All you're rationales are very logical and are things I would have never thought about. I'll be going to college in the fall, and I am definitely going to take a class in Nuclear Biology.
It is more than likely that all these NR, as you said, are intertwined. When people grow out of acne, I am wondering if its the stabilization of androgens that makes the difference and/or change of gene expression. Is there any study that says gene expression can change with time? Without any stimulation? (Naturally)
I looked up the symptoms of hypothyroidism. None of them fit me, so thats a good things!
On a side note, while I was looking up different topicals and RXR and such, and came across a medication called Targretin (Bexarotene). It is "subclass of retinoids that selectively activate retinoid X receptors (RXRs)."
http://www.rxlist.com/cgi/generic/bexarotene.htm
I wonder if this can be used for acne treatment as well, since it specifically targets the RXR receptors, same as isotretinoin.
While some people have proposed that the enzyme responsible for breaking down endogenous retinoic acid is overactive in acne patients, I tend not to believe that for most cases. First off, retinoic acid is metabolized by one of the cyp450 enzymes, a family of degradation enzymes which breakdown many natural compounds and drugs. I can't remember which one specifically is responsible for metabolizing retinoic acid. But those enzymes are very well studied. If an extremely overactive cyp450 enzyme was responsible for acne in most cases, someone would have connected the dots years ago. While there is variance among the cyp450 genes between people in how fast they metabolize products, its usually not a huge difference. Also, if that enzyme was really that overactive where retinoic acid couldn't accumulate in the skin at a normal rate, it would have other side effects on the body besides acne most likely. Those enzymes are generally multipurpose.
It is more than likely that all these NR, as you said, are intertwined. When people grow out of acne, I am wondering if its the stabilization of androgens that makes the difference and/or change of gene expression. Is there any study that says gene expression can change with time? Without any stimulation? (Naturally)
Well, I was persuing a degree in Pharmacy for a few years, but decided to switch out. I'm now a microbiology major. The education is the pharmacy school was awsome, but the idea of working at a CVS or Walgreens for the rest of my life and being a corporate whore finally got to me. I'd rather be in the lab and take a hit in the paycheck instead.
Jemini,
Really? Thats EXACTLY what I want to do. I wanna become a pharmacist, and I know that a strong grasp on chemistry and biology is needed. In you're opinion, is it difficult? What kind of classes are you required to take in order to become a pharmacist. I am enrolled in Bio and Chem, as far as science goes, in this upcoming fall.
Can you do you're on testing and research in college, on acne? I also would like to experiment with all these ideas, but I'm not sure pharmacists have the power to do that.
Best of luck man! Is there any advice you could give me?
Listener,
Cool! I noticed that anything liquid feels alot more effective than pills, not sure why. Whether that be pain killers or that green chlorophyll I've been drinking.
By the way, I would recommend it! It makes all your bowel movements feel so clean and 100%! Chlorophyll is known to detox livers, which can also help with acne!
How is the oil going?
heres a random abstract about nutrigenomics
: Acta Vet Hung. 2007 Jun;55(2):229-39.Links
Veterinary aspects and perspectives of nutrigenomics: a critical review.Fekete SG, Brown DL.
Institute of Animal Breeding, Nutrition and Laboratory Animal Science, Faculty of Veterinary Science, Szent Istvan University, H-1400 Budapest, P.O. Box 2, Hungary. [email protected]
Nutrigenomics examines nutrient-gene interactions on a genome-wide scale. Increased dietary fat or higher non-esterified fatty acids (NEFA) from starvation-induced mobilisation may enhance hepatic oxidation and decrease esterification of fatty acids by reducing the expression of the fatty acid synthase gene. The key factors are the peroxisome proliferator-activated receptors (PPARs). Dietary carbohydrates--both independently and through insulin effect--influence the transcription of the fatty acid synthase gene. Oleic acid or n-3 fatty acids downregulate the expression of leptin, fatty acid synthase and lipoprotein lipase in retroperitoneal adipose tissue. Protein-rich diets entail a shortage of mRNA necessary for expression of the fatty acid synthase gene in the adipocytes. Conjugated linoleic acids (CLAs) are activators of PPAR and also induce apoptosis in adipocytes. Altered rumen microflora produces CLAs that are efficient inhibitors of milk fat synthesis in the mammary gland ('biohydrogenation theory'). Oral zinc or cadmium application enhances transcription rate in the metallothionein gene. Supplemental CLA in pig diets was found to decrease feed intake and body fat by activating PPARgamma-responsive genes in the adipose tissue. To prevent obesity and type II diabetes, the direct modulation of gene expression by nutrients is also possible. Nutrigenomics may help in the early diagnosis of genetically determined metabolic disorders and in designing individualised diets for companion animals.
I just found out that apolipoprotein a- I gene expression could be regulated by ppar alpha.
: Eur J Pharmacol. 2006 Dec 3;551(1-3):80-6. Epub 2006 Sep 6. Links
Anti-hyperlipidemic properties of CM108 (a flavone derivative) in vitro and in vivo.Guo L, Hu WR, Lian JH, Ji W, Deng T, Qian M, Gong BQ.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China. [email protected]
Peroxisome proliferator-activated receptors (PPARs) and liver X receptor alpha are ligand-activated transcription factors that belong to nuclear receptors superfamily and are involved in the regulation of lipid metabolism. PPAR, especially PPAR-alpha, PPAR-gamma agonists and liver X receptor alpha agonists can regulate the expression or biosynthesis of some factors involved in the formation and function of HDL, such as apolipoprotein (apo) A-I and ATP binding cassette transporter A1 (ABCA1). It is well known that HDL plays an important role in the treatment of hyperlipidemia as the carrier of reverse cholesterol transport. In the present study, the anti-hyperlipidemic properties of CM108, a derivative of flavone, 9-Hydroxy-2-mercapto-6-phenyl-2-thioxo-1,3,5-trioxa-2lambda(5)-phospha-cyclopentanaphthalen-8-one, were studied. Through the transactivation assays of in vitro study, it was discovered that CM108 could activate PPAR-alpha PPAR-gamma and liver X receptor alpha at 40-150 microg/ml, which subsequently resulted in activating ABCA1 promoter and enhancing apoA-I and apoA-II production, whereas reducing apoC-III production significantly. Furthermore, after in vivo study that the hyperlipidemic rats were treated with CM108 for 4 weeks, a significant increase was found in HDL cholesterol levels (26.7%, P<0.05) and a significant decrease was also noticed in triglyceride levels (26.3%, P<0.01) at 100 mg/kg CM108 group compared with that of control animals. Meanwhile, the atherogenicity index, represented by total cholesterol/HDL ratio, was significantly reduced (P<0.01). In conclusion, CM108 can effectively elevate HDL levels and lower triglyceride levels in hyperlipidemic rats maybe by regulating a series of genes, receptors and proteins related to HDL.
since it is known that people with acne have low levels of apolipoprotein a-I sseing now its relationship to ppar alpha is also a good thing. so far ppar alpha could possibly improve two big opponents in acne, sebum production and apolipoprotein a-I or so it seems.
Interesting study. Again, acne sufferers generally have lower a1 levels. Activating ppar alpha, in conjunction with some other receptors seem increase these a1 levels.
Thetruth: Yes, a strong science background is required. At my school, pharmacy is a 6 year total program. 2 years of prereqs, then 4 years in the Pharmacy school. It wouldn't say its hard if you have a knack for science. But it all really depends. The subjects can be challenging, but being "hard" depends on the teacher, the grading and your work ethic. I will say this about being a Pharm major, when all your buddies are drinkin on a Wednesday night, you'll be up studying for your organic chem exam. Expect this to be the norm.
I will say this though. I strongly DISCOURAGE you from going into the Pharmacy. The education is rewarding, but the actual job I find, is not. You bust your ass getting this primo education, only to most likely waste it behind the counter at CVS or Walgreens. You get paid well out of college, true, but the job is monotonous, stressful and with computers now a days, the pharmacist is there "just in case." the computer systems identify the pill and look up any drug interactions, so the pharmacist is mostly just manages a team of techs and double checks the prescriptions (the techs count the pills). After working "in the system" so to speak I can see how flawed it is. Pharmacists are almost obsolete with the developing technology, they remain mostly as an antiquated safeguard. They get overpaid since they have a degree, but will almost never be required to use that education they worked hard for. I also think its messed up you get paid close to 100,000 to stand behind the counter while the World War II vet on the other side has to spend 500 bucks a month to pay for his pills, and he wonders why they are so expensive. In a few decades, traditional pharmacists will become obsolete as computers fill more and more of the roles. You could also work in a hospital which I also found to be boring as well (though better than a Chain store). You could go into research, which require more schooling after 6 years, and that is what I was going to do. But I decided I didn't want to narrow myself to just pharmaceutical research because I find it all interesting. So I switched to a microbio degree, which is basically a general "I want to work in a lab someday" degree
Thats some great research Autonomous! Thanks for sharing.
I thought though, that PPAR alpha maybe the downregulated receptor, while gamma and delta were working "regularly". Earlier in this thread, it was suggested that there maybe an unbalance between receptors which can cause acne. I know this study though involves lipid metabolism and how upregulating alpha can help control sebum.
What is currently available to act as an alpha, gamma, and liver x receptor agonist?
Thanks
Thanks for the advice Jemini.
The thing though, is that I am very interested in medicine. I would like to go into research, but as you stated, that is too many years to be in school. My family is not financially "great", so 6+ years of college will be too hefty. I thought that since I am interested in medicine, and pharmacist get paid alot to deal with medicine, why not take that route? I honestly, don't mind the idea of working behind a counter, at least not yet. I will take you're thoughts into consideration though. My goal is to get a job in something that I would enjoy, or at least, not hate.
Thanks
It's crazy though, that there are so many ideas of why we get acne, what causes excess sebum and what causes hyperkeratinization.
I guess the main stay of belief for the cause of excess sebum is either:
Lipid Metabolism
Androgens/PPARs
The causes of excess sebum are such a main focus. I wonder why no one tries to find out what causes hyperkeratinization. Obviously there is a genetic factor, but still. There are theories that sebum composition, or androgens and their interactions with PPARs cause hyperkeratinization, but there aren't that many studies on it. Maybe if there were more, we could either link the connection between excess oil and irregular shedding, or find out that real causes it.
Can anybody share some studies regarding hyperkeratinization? Thanks
That said, it seems like Accutane is really the only rthing that fixes these factors responsible in the pathogensis of acne. Isotretinoin deals with the RXR receptor, but are there any other receptors that are involved?
I'm really really tired, and am working on about 4 hours sleep in two days, so some of my stuff will be sloppy or my questions may not make sense.
It's crazy though, that there are so many ideas of why we get acne, what causes excess sebum and what causes hyperkeratinization.
I guess the main stay of belief for the cause of excess sebum is either:
Lipid Metabolism
Androgens/PPARs
The causes of excess sebum are such a main focus. I wonder why no one tries to find out what causes hyperkeratinization. Obviously there is a genetic factor, but still. There are theories that sebum composition, or androgens and their interactions with PPARs cause hyperkeratinization, but there aren't that many studies on it. Maybe if there were more, we could either link the connection between excess oil and irregular shedding, or find out that real causes it.
Can anybody share some studies regarding hyperkeratinization? Thanks
That said, it seems like Accutane is really the only rthing that fixes these factors responsible in the pathogensis of acne. Isotretinoin deals with the RXR receptor, but are there any other receptors that are involved?
I'm really really tired, and am working on about 4 hours sleep in two days, so some of my stuff will be sloppy or my questions may not make sense.
Well, it looks like I might be wrong on some things. I found a study on another messageboard about how acne sufferers might suffer from an overactive cyp450 gene.
http://www.drugtalk.com/avandia/drugthread.php/t-254590.html
Its at the bottom. Also, ppars have been linked with all sorts of skin function including keritinization, differentiation etc etc. But after skimming the studies I couldn't really tell you anymore than that. Also I know labgirl had some good posts in detail how retinoids work. I can't seem to find it now.
Autonomous,
Me too! Since I've learned that it has something to do with the RXR receptors, I've been thinking about the significance of it, and the roles it plays in the pathogenesis of acne. (Sebum and hyperkeratinization).
How come some people though, don't respond to accutane?
Jemini,
Thanks for sharing that study! I still agree though, that although they might have an overactive gene, the effects would have to be pretty "big" to cause acne, in which we would see other detrimental effects.
Retinoids don't seem to be able to penetrate the skin deep enough to make the necessary changes though. Maybe thats why it takes weeks and weeks to see any kind of improvement. Perhaps all these topicals are very effective, but the carrier isn't strong enough to penetrate the skin.
OK for everyone!
What do you guys think about adrenal disorders and acne?
Someone in this forum said taking adrenal fatigue support supplements helped him get rid of his acne.
To me this makes a lot of sense since the adrenal glands are responsible for many of the hormones of the body. Come to think about it I feel like I suffer from adrenal fatigue, by looking at the symptoms. Maybe you're hormones are out of whack and aren't in balance.
Just wanted to see what you guys thought
First, about the adrenal fatigue supplements. I would like to know whats in them to be able to fairly judge. But in general, I tend to doubt that acne is caused by overactive adrenals. True, there are certain hormones created by the adrenals. If I recall my science class, epinephrine and norepinephine are made in the medulla I think and things like cortisol and aldosterone are made in the cortex. All I know is that if any of these hormones were at abnormal levels, you would have side effects beyond acne. Epinephrine could cause acne in excess, that is why people breakout after extensive periods of stress or worry. Perhaps during finals week or you jumped out of airplanes for a living. But I really don't believe acne is caused by overactive adrenals.
My belief is that acne is actually a reflection of the genetic variance which has helped us survive over the millenia as a species. Say for instance, acne is caused by an "overactive" or over stimulated ppar, say either alpha or gamma, or even beta/delta. Variance in each one would cause people to have different body shapes. Say one person had too much ppar gamma, not only would they might have acne, but they would be more likely to store fat, (ppars are mainly associated with energy metabolism). PPar gamma agonist drug Avandia is used for diabetics. People with high blood sugar need to get the sugar out, so by stimulating ppar gamma causes one to pull the sugar out of the blood and create fat instead. Say way back in the cave man days there was little food around, those who were able to store fat easier might actually have a survival edge. I'm not saying this specific instance is the case, but the idea that the tendency to have acne is actually an expression of some sort of genetic variance which might offer some of the population a better chance to survive, at least in terms of Darwinian evolution.
I wonder if the rxr receptor actually has anything to do with acne control at all, and not just its ability to form heterodimers with other receptors. To test the idea, one could design a drug that bound just as tightly to the rxr or rar receptors as accutane, but didn't cause the same powerful transcription effect. In otherwords kind of like a partial agonist/antagonist. That way it would bind up the other nuclear receptors, but would only cause a "signal" at the retinoid receptor at approximately normal levels. Ah, if only such a chemical existed. If this chemical were to exist, it could be just as effective as accutane, but perhaps with fewer side effects. It would still probably raise triglycerides though.
Jemini,
Here is what I am taking for adrenal fatigue.
http://www.enzy.com/go/EnzymaticTherapy/pr...;partcode=04035
Thats a pretty interesting theory. So maybe acne is just another "side effect" of a larger genetic predisposition?
I checked out the pinned retinoids thread, where RARs and RXRs were discussed. Well I guess these receptors are found in the skin and thats how retinoids help. They are agonists for these receptors and normalize cell differenitiation. So yeah, maybe since these agonists bind to these receptors, ppars are not able to form them.
What are your thoughts on topical isotretinoin?
Is it your belief (you three) that the aspect of our physiology that accutane changes is in fact the aspect that is worng in the first place?
I mean things like benzoyl peroxide etc.. are not fixing the actual problem. (Our skin isn't oily and keratinous because it is too low pH, yet the acidic peeling effect of BP will still aid in desquamation)
Follow through question is: If it corrects the underlying problem then why does it have certain side effects that people with naturally clear skin don't get?
Like dry eyes and joint pains etc.. Is it to do with the large dosage.... I'mnot sure myself, but the 13-cis-Retinoic Acid supplementation idea is starting to really peak my interest. I've got uni coming up and i really don't want to waste years waiting to try isotretinoin and then finally go on it and be like: 'dayum why the hell didn't i do this 6 years ago?!?!'
Btw the fish oil is going okay. I've been abroad and had a higher glycemic load than usual. I have been consistent with the fish oil though, 7 grams omega 3 a day still. I can definitely say i don't think it is making i worse like i thought last time. I've only been doing it for just over two weeks so far and i've had some big nights out and diet blowouts along the way so i got some hope for it.
I discontinued chromium because i no longer think insulin resistance is an important enough underlying factor.
Jemini,
Here is what I am taking for adrenal fatigue.
http://www.enzy.com/go/EnzymaticTherapy/pr...;partcode=04035
Thats a pretty interesting theory. So maybe acne is just another "side effect" of a larger genetic predisposition?
I checked out the pinned retinoids thread, where RARs and RXRs were discussed. Well I guess these receptors are found in the skin and thats how retinoids help. They are agonists for these receptors and normalize cell differenitiation. So yeah, maybe since these agonists bind to these receptors, ppars are not able to form them.
What are your thoughts on topical isotretinoin?