83 replies to this topic

[thetruth24]

I came across berberine in this thread:

http://www.acne.org/messageboard/index.php...erine&st=20.

They posted the same studies as autonomous. I guess PPARs play a pretty big role in acne.

There is some really good info by flipside. Check it out

[AutonomousOne1980]

Autonomous, sweet research!

I also thought you're other studies were interesting. So basically, you're theory is that the ALPHA receptor is responsible for the creation of apolipoprotein a1? I remember you stating that acne maybe a way of our bodies saving us from a heart attack. Accutane suppresses these glands, which is why our enzymes or something go up. It makes really good sense. The only thing is that I can't understand why then, would acne only start up at puberty, and for most people, end after it??

My point was to show that acne is more then just a sebaceous gland skin problem and that their are whole systematic changes involved,such as Abnormal cholesterol functioning and also show that accutanes efficacy goes beyond just the skin and corrects abnormal lipid metabolism, and how ppars are involved in both improving abnormal lipd metabolism, influencing the sebaceous gland and to show how big of a role ppars may play in acne.

[thetruth24]

Ahhh alright, gotcha!

So basically chlorophyll, fish oil, berberine and possibly resveratrol as natural supplements.

I think the reason this stuff would work better topically as because it would applied locally and directly affect the receptors in the glands responsible for acne, given that it has a proper vehicle and is readily and easily absorbed.

[Listener]

Also, could you give this little desripition of sesamin a read through: http://www.bodybuilding.com/store/san/ses.html

Sure you can make clearer sense of how it connects to acne than i can. I've heard of a lot of anecdotal claims that it definitely helped people with acne by a noticeable amount.

oh yea! sesamin also activates ppar alpha, forgot about that one as well.

where did you read these claims?

They are actually pretty interesting. It seems reliable because most of these people were taking this for bodybuilding purposes and not to do with acne yet they still noticed the difference in the skin therefore i believe it must have been significant:
FYI Sesathin is a brand name of Sesamin that is commonly used in the bodybuilding forums due to its fat burning ability. (supposedly)

'Adding Sesathin and moderately high dose (4tbsp daily) flax oil to my diet* has helped my acne more than anything else I've ever tried, including prescription medications.

* Prior to this I was using fish and olive oil only, as well as getting in a decent amount of dietary fats from nuts, meats, and dairy.'
This quote is from a thread which has a reasonably informative first post also. Ndnromeo should find the flax part interesting i think.
http://www.avantlabs.com/forum/index.php?showtopic=21116

Lots of interesting anecdotal claims: http://forum.bodybuilding.com/showthread.php?t=606334

Started by the same guy but has other posters there saying they had similar results: http://forum.bodybuilding.com/showthread.php?t=571184

A post from that thread that may interest specifically you Autonomous : 'Sesamin is a delta-5 desaturase inhibitor. When GLA, a omega-6 fatty aicd, is absorbed into the blood, it is first broken down to the biologically active di-homo gamma linolenic acid (DGLA). From there DGLA can go in two directions, one of them highly beneficial, the other possibly detrimental.

The beneficial route involves the DGLA being converted into an inflammatory-suppressing hormone-like substance called prostaglandin E1. The undesirable route involves DGLA being converted into arachidonic acid, which is a precursor to pro-inflammatory prostaglandin E2 and leukotriene B4.

Sesame lignans suppress the enzyme (delta-5 desaturase) that converts DGLA into arachidonic acid. By blocking the undesirable enzyme (delta-5 desaturase), more DGLA is available for conversion into beneficial prostaglandin E1.

Products that lowers leukotriene B4 like a 5-lipooxygenase inhibitor has been shown to help acne. Also the same with PGE2 and COX-2 inhibitor. Look at this picture. http://www.lef.org/magazine/mag2004/..._gla_02_lg.gif


Sesamin also raises the good form of vitamin E, gamma tocopherol. The cheap and most common of Vitamin E,alpha-tocopherol, will just give you acne problems. This has just recently been discovered so it takes some time before the old vitamin E products are of the market. But there are many now out there with the right ratios of the different tocopherols.'




Random post from a bodybuilding forum: 'Sesamin works wonders for acne as well as vitamin b-5 I can vouch for both...drinking tons of water and eating your fruits and vegetables helps too..water is the best thing imo'

Pretty interesting huh?

Kinda makes it seem like maybe we aren't searching in vain .... I'm interested to see the results of the flax seed experiment of Ndn's.

[thetruth24]

I know I probably stated this before, but on wikipedia it says:

"All PPARs dimerize with the retinoid X receptor (RXR) and bind to specific regions on the DNA of target genes."

Correct me if I am wrong, but doesn't isotretinoin affect the RXR? If so, it leaves PPARs unable to dimerize with anything, and thats why accutane works?

It just puzzles me that every sign points to androgens, as the real culprit of acne. I mean Kids don't have acne. They touch their face with greasy hands, eat horrible food, but have clear skin! It is only when they hit puberty and hormones surge through their bodies that acne beings to show up. Likewise, many people outgrow acne, relatively close to when puberty ends.

Also, although the key could be, to find something to bind to these receptors, we are unsure of what it would do. There is a possibility it would increase/decrease sebum.

Androgens MUST play a role in PPAR dimerization.

[jemini]

It seems that resveratrol, green tea, chlorophyll and other phytonutrients all seem to have some overlapping properties. If I recall correctly, green tea is an antioxidant, cox/lox inhibitor, dht inhibitor etc etc. I agree that PPAR's are probably at the forefront of the acne problem. PPAR's are responsible for lipid metabolism in the body as well as sebaceous control in the skin. IT is clear that sesamin and fish oil have some effect on the ppar's. Both generally active ppar alpha which tends to be affiliated with its anti-inflammatory effects. I noticed that when I took fish oil and sesamin (on separate occasions) both DEFINATALY made me oilier. Which makes sense since ppar agonists increase sebum production. Also, artificial ppar agonists like Avandia for diabetes are also known to increase sebum production. So then why do some people improve on fish oil and sesamin and dry up while others get worse? I don't know. My best guess is that in acne patients, there is either an imbalance to the ppar's expressed. Perhaps an overactive or over expressed ppar gamma, or even beta delta is to blame. Ppar gamma tends to get activated by proinflammatory ligands and oxidized fats. Perhaps naturally occurring proimflammaytory ligands are enough to cause a greater response in acne patients than non sufferers. Perhaps some acne patients have ppar gamma upregulated due to exposure to some sort of allergen or toxin. What is known is that our body tends to balance out the expression of ppars, so by increasing the expression of antimflammatory ppar alpha through supplements, that mighe be enough to downregulate ppar gamma? Maybe for some people this "imbalance" is worse than others which might explain why some people get oiler at first or get an initial breakout. The supplements are activating and upregulating ppar alpha before our body can slowly downregulate the other ppars?

I'm personally believe that accutane resets the ppars to zero. That is why people stay clear at least temporarily after a course even in the presense of foods, allergens or toxins that make them breakout. It is only over the course of weeks/months that our body slowly upregulates the proinflammatory receptors and causes our acne to remerge. So perhaps taking a ppar alpha agonist after a course of accutane would be the most practical way to keep acne at bay? Or perhaps taking enough fish oil/sesamin for long enough at the right dosage might be enough to slowly change our receptors over the passing months?

This is only a general hypothesis based on what I have observed. I am not a scientist, doctor and anyone in any position to be giving medical advice. Please, feel free to correct me, disprove me make fun of me, whatever.

p.s. sorry for changing the topic

[thetruth24]

That is very interesting Jemini.

But I still can't understand then, why people outgrow acne. Do these PPARs naturally stabilize? Some people on accutane, I believe 50% are cured after one course! Obviously after discontinuing isotretinoin, it will leave you're system. Do you think that, taking those dosages at extended periods of time cause a permanent change in these receptors?

Autonomous noted that the alpha receptor is responsible for creating a "carrier" that collects fat which is brought to the liver to be broken down. So there are conflicting ideas about the actual function of these receptors regarding sebum. I wonder what would happen if you shut down these receptors.

I forgot to add, but a while back I had clear skin. I played football, and with full gear, specifically head gear, pressing on your forehead, temples, and chin, added with sweat and bacteria, my skin still was clear. It was until I started experimenting with testosterone boosters, which made me break out horribly.

Another thing that has been knawing at my ankle. What about hyperkeratinization? I've come across numerous posts where people have oily skin but no acne. Whats the deal?

Here's a quote:
"While any hormonal excess can promote acne, the male hormones (which are present in both males and females, only in differing amounts) are particularly notorious for stimulating the cells in the hair follicle to produce more keratin (a hard protein that forms hair, skin and nails)."

Also, check this link: http://www.blackwell-synergy.com/doi/abs/1...1997.d01-1162.x

From personal experience and research, PPARs and androgens MUST be what is causing acne. There cannot be acne if there is no improper shedding of skin cells. Then again, it maybe sebum composition that affects keratinization.

I would also like to add, that, although some people with acne have normal levels of androgens in their bloodstream, they have a higher amount of it in the local area of the sebaceous glands.

One more interesting study on androgens and sebum + hyperkeratinization:
http://www.dms.moph.go.th/inderm/Journal/C...20no2%20p92.pdf

[jemini]

While I'm no expert on nuclear biology or ppars, I can offer my opinion. In all honesty, I don't think accutane cures acne, but merely buys a person time for their hormones/ppars or whatever is out of whack in their system to return to normal. It clears most people the first time, since most people take it during puberty, a time of insulin resistance when acne is more likely to be prevelent. The accutane would buy them time until they grow out of puberty. Permanent remission rates in adulthood tend not to be so good. If puberty related insulin resistance isn't the cause, then accutane probably won't "buy you time" until your body fixes yourself.

I also remember reading a study, though I don't have the link that ppar's have been linked to skin's keritinization functions. Though I couldn't tell you how. All I can suggest is that you google ppar's and just try to suck up as much information as you can about them from different studies. The problem is even still, ppar's remain at the cutting edge of research and no one is able to tell the full story on what they do, how they work, and how they play with each other and other receptors.

My guess with hormones is that they must play some sort of indirect role. Androgens (namely testosterone) binding to the AR must affect ppar binding or expressivity. I do know that ppars do form dimers with other nuclear receptors, so the expression and binding of those receptors may also have an effect. Its problems like these that make nuclear biology so hard and why there still isn't any cure for acne. I don't believe in any of those pharmaceutical conspiracies people rave about on this site, and I also believe in the good nature of most scientists. If a scientist came across a cure, I believe they would share it with the world. And though there is alot of money in treatment of acne, if someone comes up with a cure, not only would that company become EXTREMELY rich, it would also help to put rival companies out of business.

As people have said before, acne is a symptom of an underlying cause. There could be many different causes. Only a few years ago, acne was thought to be caused by bacteria, which was found rarely to be the case. It turns out antibiotics worked coincidentally because they also exerted antinflammtory effects on specific enzymes. That is why low dose antibiotics (below bacteriocidal concentrations) are being researched for acne too. Check out the drug incyclinide. http://rosacea-support.org/incyclinide-col...x-gets-nih.html
Its a drug in development that has tetracycline like antimflammatory effect, but does not kill the bacteria, so there is no risk of immune strains, or kill of the probiotics in the gut and other problems associated with antibiotic therapy. I believe you'll be hearing alot about this drug in the next few years.

Anyway, I forgot what I was talking about. I'll save the ranting for another time

[AutonomousOne1980]

Ahhh alright, gotcha!
So basically chlorophyll, fish oil, berberine and possibly resveratrol as natural supplements.

in a hopefull world yes these supplements could help you, they have at least been helping me so far, hell no i aint cured but we will see what happens in another six months or so.

I think the reason this stuff would work better topically as because it would applied locally and directly affect the receptors in the glands responsible for acne, given that it has a proper vehicle and is readily and easily absorbed.

you are free to think anything you want i guess, if you want to find out the truth give it a shot.

[AutonomousOne1980]

I know I probably stated this before, but on wikipedia it says:

"All PPARs dimerize with the retinoid X receptor (RXR) and bind to specific regions on the DNA of target genes."

Correct me if I am wrong, but doesn't isotretinoin affect the RXR? If so, it leaves PPARs unable to dimerize with anything, and thats why accutane works?

It just puzzles me that every sign points to androgens, as the real culprit of acne. I mean Kids don't have acne. They touch their face with greasy hands, eat horrible food, but have clear skin! It is only when they hit puberty and hormones surge through their bodies that acne beings to show up. Likewise, many people outgrow acne, relatively close to when puberty ends.

Also, although the key could be, to find something to bind to these receptors, we are unsure of what it would do. There is a possibility it would increase/decrease sebum.

Androgens MUST play a role in PPAR dimerization.

well yes sex hormones allow for enhanced cellular growth and affects sebaceous glands, but who is to say that if you did not enter puberty, your acne wouldnt have continued to get worse due to other inlfuences on sebaceous glands, and the fact you were going through puberty, was just another reason your acne was really bad.

that being said, why was my acne worse at 25 then it was when i was 20? I was way out of puberty by then, yet my acne got worse, why is that?

Also androgen levels in males are normal compared to others the same age without acne, and dht alone have little effect on the sebaceous gland.

I do not think we have strong enough reasons to conclude 100% certainty that androgens interfere with ppars relationship to rxr.But androgens definitly play a major role in adolescent acne, as for adult acne it may be more of something else.

[AutonomousOne1980]

It seems that resveratrol, green tea, chlorophyll and other phytonutrients all seem to have some overlapping properties. If I recall correctly, green tea is an antioxidant, cox/lox inhibitor, dht inhibitor etc etc. I agree that PPAR's are probably at the forefront of the acne problem. PPAR's are responsible for lipid metabolism in the body as well as sebaceous control in the skin. IT is clear that sesamin and fish oil have some effect on the ppar's. Both generally active ppar alpha which tends to be affiliated with its anti-inflammatory effects. I noticed that when I took fish oil and sesamin (on separate occasions) both DEFINATALY made me oilier. Which makes sense since ppar agonists increase sebum production. Also, artificial ppar agonists like Avandia for diabetes are also known to increase sebum production. So then why do some people improve on fish oil and sesamin and dry up while others get worse? I don't know. My best guess is that in acne patients, there is either an imbalance to the ppar's expressed. Perhaps an overactive or over expressed ppar gamma, or even beta delta is to blame. Ppar gamma tends to get activated by proinflammatory ligands and oxidized fats. Perhaps naturally occurring proimflammaytory ligands are enough to cause a greater response in acne patients than non sufferers. Perhaps some acne patients have ppar gamma upregulated due to exposure to some sort of allergen or toxin. What is known is that our body tends to balance out the expression of ppars, so by increasing the expression of antimflammatory ppar alpha through supplements, that mighe be enough to downregulate ppar gamma? Maybe for some people this "imbalance" is worse than others which might explain why some people get oiler at first or get an initial breakout. The supplements are activating and upregulating ppar alpha before our body can slowly downregulate the other ppars?

I'm personally believe that accutane resets the ppars to zero. That is why people stay clear at least temporarily after a course even in the presense of foods, allergens or toxins that make them breakout. It is only over the course of weeks/months that our body slowly upregulates the proinflammatory receptors and causes our acne to remerge. So perhaps taking a ppar alpha agonist after a course of accutane would be the most practical way to keep acne at bay? Or perhaps taking enough fish oil/sesamin for long enough at the right dosage might be enough to slowly change our receptors over the passing months?

This is only a general hypothesis based on what I have observed. I am not a scientist, doctor and anyone in any position to be giving medical advice. Please, feel free to correct me, disprove me make fun of me, whatever.

p.s. sorry for changing the topic

ok, now thats some damn good thinking! and it is known that accutane upregulates rxr receptors and makes your skin more sensitive to natural retinoic acid created intercellularly allowing the cells to return to a normal controlled growth cycle. But then the question remains as to why the effect can wear off.

I havent read any studies that even looked at how accutane affects the ppar receptors but your mention of ppar gene regulation has got me thinking.

so i remembered this study:

1: J Mol Med. 2006 Jan;84(1):75-87. Epub 2005 Dec 31. Links
Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands.Alestas T, Ganceviciene R, Fimmel S, Müller-Decker K, Zouboulis CC.
Department of Dermatology, Charité Universitaetsmedizin Berlin, Campus Benjamin Franklin, Fabeckstrasse 60-62, 14195 Berlin, Germany.

The expression of enzymes involved in leukotriene and prostaglandin signalling pathways, of interleukins 6 and 8 and of peroxisome proliferator-activated receptors in sebaceous glands of acne-involved facial skin was compared with those of non-involved skin of acne patients and of healthy individuals. Moreover, 5-lipoxygenase and leukotriene A(4) hydrolase were expressed at mRNA and protein levels in vivo and in SZ95 sebocytes in vitro (leukotriene A(4) hydrolase > 5-lipoxygenase), while 15-lipoxygenase-1 was only detected in cultured sebocytes. Cyclooxygenase-1 and cyclooxygenase-2 were also present. Peroxisome proliferator-activated receptors were constitutively expressed. Enhanced 5-lipoxygenase, cyclooxygenase 2 and interleukin 6 expression was detected in acne-involved facial skin. Arachidonic acid stimulated leukotriene B(4) and interleukin 6 release as well as prostaglandin E(2) biosynthesis in SZ95 sebocytes, induced abundant increase in neutral lipids and down-regulated peroxisome proliferator-activated receptor-alpha, but not receptor-gamma1 mRNA levels, which were the predominant peroxisome proliferator-activated receptor isotypes in SZ95 sebocytes. In conclusion, human sebocytes possess the enzyme machinery for functional leukotriene and prostaglandin pathways. A comprehensive link between inflammation and sebaceous lipid synthesis is provided.


so according to this study, in acne skin there is an increased pathway for the creation of arachidonic acid and proinflammatroy eicosanoids such as ltb4, pge2 and il-6. It also states that the production of these eicosanids from AA, down regulates ppar alpha and increases lipid production. I must have missed the down regulate ppar alpha before when reading this but this would be the last step to making acne happen. For example, as ppar alpha is continually down regulated from increased inflammatory eicosanoids, that could mean less ppar receptors to activate rxr and induce apoptosis, causing sebacous cells to keep growing and produce more lipids. accutane seems to skip ppar route of activated rxr by going straight to the rxr receptor, when all we may have to do is upregulate ppar alpha, or stop whatever is downregulating it, which could be the production of proinflammatory eicosanoids from Arachidonic acid.

some supporting studies

Prostaglandins Other Lipid Mediat. 2007 May;83(3):188-97. Epub 2007 Jan 17. Links
Pharmacotherapy of diseases mediated by 5-lipoxygenase pathway eicosanoids.Rubin P, Mollison KW.
Critical Therapeutics, Inc., 60 Westview Street, Lexington, MA 02421, USA. bjeffres@crtx.com


Inflammatory eicosanoids generated by the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism are now known to have at least 6 receptors: OXE, which recognizes 5-HETE and 5-oxo-ETE; a putative receptor recognizing a potent 5-oxo-ETE metabolite, FOG(7); the LTB(4) receptors, BLT1 and BLT2; the cysteinyl leukotriene receptors, CysLT(1) and CysLT(2), which recognize leukotrienes LTC(4), LTD(4), LTE(4) and LTF(4). The 5-LO pathway is activated in many diseases and invokes inflammatory responses not affected by glucocorticoids, but therapy with selective BLT1 or CysLT(1) antagonists in asthma has met with variable success. Studies show that 5-LO pathway eicosanoids are not primary mediators in all cases of asthma, but may be especially important in severe persistent asthma, aspirin- and exercise-induced asthma, allergic rhinitis, COPD, idiopathic pulmonary fibrosis, atherosclerosis, atopic dermatitis, acne and ischemia-related organ injury. These disorders appear to involve multiple 5-LO pathway eicosanoids and receptor subtypes, suggesting that inhibition of the pathway at the level of 5-LO may be necessary for maximal efficacy.

[AutonomousOne1980]

While I'm no expert on nuclear biology or ppars, I can offer my opinion. In all honesty, I don't think accutane cures acne, but merely buys a person time for their hormones/ppars or whatever is out of whack in their system to return to normal. It clears most people the first time, since most people take it during puberty, a time of insulin resistance when acne is more likely to be prevelent. The accutane would buy them time until they grow out of puberty. Permanent remission rates in adulthood tend not to be so good. If puberty related insulin resistance isn't the cause, then accutane probably won't "buy you time" until your body fixes yourself.

I also remember reading a study, though I don't have the link that ppar's have been linked to skin's keritinization functions. Though I couldn't tell you how. All I can suggest is that you google ppar's and just try to suck up as much information as you can about them from different studies. The problem is even still, ppar's remain at the cutting edge of research and no one is able to tell the full story on what they do, how they work, and how they play with each other and other receptors.

My guess with hormones is that they must play some sort of indirect role. Androgens (namely testosterone) binding to the AR must affect ppar binding or expressivity. I do know that ppars do form dimers with other nuclear receptors, so the expression and binding of those receptors may also have an effect. Its problems like these that make nuclear biology so hard and why there still isn't any cure for acne. I don't believe in any of those pharmaceutical conspiracies people rave about on this site, and I also believe in the good nature of most scientists. If a scientist came across a cure, I believe they would share it with the world. And though there is alot of money in treatment of acne, if someone comes up with a cure, not only would that company become EXTREMELY rich, it would also help to put rival companies out of business.

As people have said before, acne is a symptom of an underlying cause. There could be many different causes. Only a few years ago, acne was thought to be caused by bacteria, which was found rarely to be the case. It turns out antibiotics worked coincidentally because they also exerted antinflammtory effects on specific enzymes. That is why low dose antibiotics (below bacteriocidal concentrations) are being researched for acne too. Check out the drug incyclinide. http://rosacea-support.org/incyclinide-col...x-gets-nih.html
Its a drug in development that has tetracycline like antimflammatory effect, but does not kill the bacteria, so there is no risk of immune strains, or kill of the probiotics in the gut and other problems associated with antibiotic therapy. I believe you'll be hearing alot about this drug in the next few years.

Anyway, I forgot what I was talking about. I'll save the ranting for another time

rarely would a purely criminal mind by willing to go through such pain of reading and learning and studying biology just to scam someone,to find a cure for a disease requires a motivation much deeper then that, crooks would much rather rob a bank or steal your wallet. The likeliness for a conspiracy is minimal it seems, anything is possible but a scientist witholding a cure would be highly improbable.

[thetruth24]

Autonomous,

That we will never know. I am just speaking from anecdotal experiences. My friend for example, had very bad acne for about 2-3 years of high school. All of a sudden, when he hit 18 and so forth, his acne started clearing up drastically. I am just guessing his hormones calmed down and his acne subsided. To this day, he will still get the occasional pimple, but nothing severe like before.

Again, I can't answer why you're acne got worse. But like you said maybe the root cause of you're acne is different since you are way past puberty.

When you say the androgen levels in those males are normal, are you speaking about the levels in the bloodstream or in the local area of the sebaceous glands. There are studies where testosterone levels were the same in bloodstream, but people with acne had a more considerable amount in the local area of acne. Just a thought though.

BTW, I am only 17 years old. I am still in that growing stage of my life. That, and the fact that I experimented with testosterone boosters earlier. (Broke me out pretty bad)

[thetruth24]

Hey Guys,

I came across this very interesting study on acne and androgens.

It is a very long read, but well worth it.

http://www.patentstorm.us/patents/5519039-description.html

[AutonomousOne1980]

crazy shit about chlorophyll i didnt expect to find

Mol Biol Cell. 1996 Aug;7(8):1153-66. Links
Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR.Kitareewan S, Burka LT, Tomer KB, Parker CE, Deterding LJ, Stevens RD, Forman BM, Mais DE, Heyman RA, McMorris T, Weinberger C.
Orphan Receptor Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.

RXR is a nuclear receptor that plays a central role in cell signaling by pairing with a host of other receptors. Previously, 9-cis-retinoic acid (9cRA) was defined as a potent RXR activator. Here we describe a unique RXR effector identified from organic extracts of bovine serum by following RXR-dependent transcriptional activity. Structural analyses of material in active fractions pointed to the saturated diterpenoid phytanic acid, which induced RXR-dependent transcription at concentrations between 4 and 64 microM. Although 200 times more potent than phytanic acid, 9cRA was undetectable in equivalent amounts of extract and cannot be present at a concentration that could account for the activity. Phytanic acid, another phytol metabolite, was synthesized and stimulated RXR with a potency and efficacy similar to phytanic acid. These metabolites specifically displaced [3H]-9cRA from RXR with Ki values of 4 microM, indicating that their transcriptional effects are mediated by direct receptor interactions. Phytol metabolites are compelling candidates for physiological effectors, because their RXR binding affinities and activation potencies match their micromolar circulating concentrations. Given their exclusive dietary origin, these chlorophyll metabolites may represent essential nutrients that coordinate cellular metabolism through RXR-dependent signaling pathways.



could this actually be the dietary natural equivelant to accutane?

when i first discovered phytanic acid and its ability to affect ppar alpha, i thought it was peculiar that it was derived from the green pigment in plants, when you think of this pigment it is pretty much the universal color of life like in spring when everything turns green again you see everything coming back to life, i was thinking to myself why our creator made this pigment so abundant? well of course i know that chlorophyll helps plants convert sunlight into energy but now even to learn that it may also affect rxr receptors directly as well as through ppar pathway is just cool.

As we know through studying retinoids that when 13-cis retinoic acid binds to rxr it restores the cell to homeostasis or makes the cell stable by inducing apoptosis or cell death, an organism that is alive and well is basically a collection of cells that are in homeostasis and is a stable organism, so life=homeostasis and death=uncontrolled proliferation such as cancers that kill most people and also similar to the uncontrolled proliferation of keratinocytes and sebaceous glands, so acne could be one step closer to death since their is a lack of homeostasis, its as though phytanic acid or phytol or chlorophyll could be natures way of stabilizing life on planet earth, as rxr agonists are also used for many cancers as well as acne and psoriasis which are all cell that have lost homeostasis and all are conditions that are treated very well with retinoids.

[thetruth24]

Autonomous,

That is indeed very interesting!

"Structural analyses of material in active fractions pointed to the saturated diterpenoid phytanic acid, which induced RXR-dependent transcription at concentrations between 4 and 64 microM. Although 200 times more potent than phytanic acid"

What exactly does this mean??

You also stated:
"13-cis retinoic acid binds to rxr it restores the cell to homeostasis or makes the cell stable by inducing apoptosis or cell death. To my understanding isotretinoin helps acne, so why would it induce cell death, which as you stated, is "uncontrolled proliferation"?

You're theory makes a lot of sense though. I wonder how much chlorophyll would need to be ingested to have a noticeable effect.

Here's something else I found of Chlorophyll and acne:
Chlorophyll and lemon

Chlorophyll is one of the best ways to detoxify the colon fast. Your colon needs to be detoxified constantly to prevent toxins from getting into your blood and seeping into your facial skin where they can create acne. It also helps the skin keep healthy by acting as an

* antioxidant

* anti-inflammatory

* anti-microbial agent

* absorber of heavy metals in the colon

Here are some of the benefits you will get from drinking chlorophyll,

* Heals open wounds inside your body

* Increases re-growth of tissues

* Helps to heal sores in your mouth

* Acts as a antiseptic

* Destroys bacteria

* Brings more oxygen to your cells

* Give protection from low levels of radiation such as TV, computers, microwaves, and hospital equipment

* Reduces toxins in the colon and body

* Helps to purify the liver

* Helps sores heal faster

* Reduces pain from inflammation

[AutonomousOne1980]

"13-cis retinoic acid binds to rxr it restores the cell to homeostasis or makes the cell stable by inducing apoptosis or cell death. To my understanding isotretinoin helps acne, so why would it induce cell death, which as you stated, is "uncontrolled proliferation"?

well the problem with acne is their is an overproduction of oil and problems with skin cells shedding, the cells dont die on time, or when they are supposed to so the sebaceous glands grow larger and produce more oil, while the skin cells also divide and grow so fast that their is no control over the life and death process of a cell then you get acne when the walls of the follicle are either so thick that sebum doesnt escape or skin has completely blocked it or dead skin cells are clumping together and mixing with sebum eventually forming a plug.

The life and death cycle of a cell should be like clock work for everything to function properly, and for their to be stability or homeostasis, the goal is harmony.

from Wiki:

Homeostatic Imbalance
Much disease results from disturbance of homeostasis, a condition known as homeostatic imbalance. As it ages, every organism will lose efficiency in its control systems. The inefficiencies gradually result in an unstable internal environment that increases the risk for illness. In addition, homeostatic imbalance is also responsible for the physical changes associated with aging. Even more serious than illness and other characteristics of aging, is death. Heart failure has been seen where nominal negative feedback mechanisms become overwhelmed, and destructive positive feedback mechanisms then take over


so you could say that our bodies are just breaking down, there is a system that is not working properly, the reason why we do get acne could be because its the weakest link in our genes, while other people will have some other system fail them in due time. acne is easier to see, but what if all those other people with shitty diets have something else going on inside, something slowly breaking down but you cant see inside their body so you assume they are healthy and they do to, but ive read that cancer begins with the uncontrolled proliferation cells until one day the cells become mutated from carcinogens and turns the cell cancerous and now you have mutated and unhealthy cells growing in your body, not sure if thats exactly how it works but its something like that.

[thetruth24]

Ahhh alright, thanks for clarifying that up a bit.

Just to be straight, when 13 cis retinoic acid binds to RXR, the cells become stable and the life and death cycle is returned to normal?

I came across this website:
http://www.leaddiscovery.co.uk/target-disc...Med-030306.html

"Since RXR forms heterodimers with both PPARalpha and PPARgamma blocking RXR may produce a phenotype that shares some similarities with PPARalpha deletion and others with PPARgamma deletion. Since therapeutic candidates that target PPAR may confer most benefit in the context of diabetes and obesity if they activate PPARalpha and/or block PPARgamma it is conceivable that RXRalpha antagonists may be of use if they are selective for RXR:PPARgamma heterodimers and fail to impede RXR:PPARalpha mediated effects. This is supported in part by recent research showing that the dual antagonism of RXR and PPARgamma decreases triglyceride content, potentiates leptin's effects and increased fatty acid combustion and energy dissipation, thereby ameliorating diet-induced obesity and insulin resistance. Molecules that block RXR:PPARgamma and stimulate RXR:PPARalpha dimers may represent an even better approach."

Looks like PPARs and RXRs go hand in hand. Isotretinoin binds to RXR and does not allow PPARs to form dimers?

So basically we need to upregulate PPAR alpha? What are the roles of delta and gamma?

[AutonomousOne1980]

check out this video on ppars

http://www.youtube.com/watch?v=ItEFZvqmjhQ

[thetruth24]

That was a very informative and sorta fun watch! Thanks for sharing.

I went to Vitaminshoppe today to pick up some Cholorophyll and ended up getting something called the Cholor-Combo.

It contains:


Amount Per
Serving

Sodium (An Electrolyte)

Chlorophyll (Sodium Copper Chlorophyllins)(From Alfalfa Leaves)(Medicago Sativa)

CAPE ALOE (WHOLE)(ALOE SOLCATA)

ALLANTOIN

HERBAL COMPLEX BLEND PEPPERMINT LEAVES (MENTHA PIPERITA), FENNEL SEED (FOENICULUM VULGARE), GINGER ROOT (ZINGIBER OFFICINATE), RED RASPBERRY LEAVES (RUBUS STRIGOSUS)

....

Allantoin from Wiki:

"Manufacturers cite several beneficial effects for allantoin as an active ingredient in over-the-counter cosmetics: a moisturizing and keratolytic effect, increasing the water content of the extracellular matrix and enhancing the desquamation of upper layers of dead skin cells, increasing the smoothness of the skin; promotion of cell proliferation and wound healing; and a soothing, anti-irritant, and skin protectant effect by forming complexes with irritant and sensitizing agents."

Lets see how this works out!