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AutonomousOne1980

retinoic acid metabolism, accutane and beta carotene

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so one of the theorys as to why we have acne is that some acne sufferers have an overactive enzyme inthe skin that breaks down retinoic acid faster then it can be created, and therefore allows the skin to grow abnormally, it allows an over growth of sebaceous cells and skin cells causing the sebaceous glands to produce more sebum and the skin cells to multiply exponentially and then what you have is an environment where comedones can plug the follicle and create acne.

the enzyme that is over active is known as cyp26ai

Skin Retinoid Concentrations Are Modulated by CYP26AI Expression Restricted to Basal Keratinocytes in Normal Human Skin and Differentiated 3D Skin Models. june 2006

1Department of Dermatology and Allergology, University Hospital of the RWTH Aachen, Aachen, Germany.

Cellular levels of all-trans retinoic acid (RA) are meticulously regulated utilizing an array of systems to balance uptake, biosynthesis, catabolism, and efflux transport. Metabolic transformation of all-trans RA to 4-hydroxylated RA appears to be primarily catalyzed by the cytochrome P450 (CYP) 26AI. Analysis of monolayer cultures of normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts by quantitative real-time PCR and reverse transcription-PCR revealed no basal levels of CYP26AI mRNA expression, whereas specific transcripts were detectable following addition of 10(-6) M all-trans RA. Immunofluorescence and Western blot analysis showed a weak expression of CYP26AI in NHEK, which was increased by stimulation with all-trans RA. Using a newly developed peptide antibody, we further examined the localization of CYP26AI expression in normal skin and three-dimensional (3D) skin models. In contrast to cell culture monolayers where CYP26AI was only weakly detectable, strong constitutive expression of CYP26AI in vivo and in organotypic culture was found to be restricted to basal epidermal keratinocytes, as well as eccrine sweat glands and sebaceous glands. These studies verify the capacity of human skin to metabolize RA, although substantial differences exist in CYP expression between normal skin and 3D skin models compared to monolayer cultures. Complex metabolic processes that maintain retinoid homeostasis may therefore be better studied in model systems more closely resembling in vivo skin. In light of our prior studies documenting the functional activity of RA metabolites, expression of CYP26 in the sebaceous gland epithelium supports the suggestion that altered RA metabolism may be involved in the pathogenesis of acne.Journal of Investigative Dermatology advance online publication, 15 June 2006; doi:10.1038/sj.jid.5700432

my theory was and i guess still is that retinoic acid production in the cell can be increased by taking high amounts of beta carotene.

when beta carotene is ingested it is absorbed through the intestinal walls and some of it is converted into retinal and some of it is absorbed in the blood stream as beta carotene to be absorbed by cells directly. http://pharmrev.aspetjournals.org/cgi/cont...ull/50/2/315/F4

From my research on accutane i know that 13-cis retinoic acid is absorbed into cells and turns into all trans retinoic acid and binds to retinoid receptors. It looks as though beta carotene has the exact same ability to do this. this diagram not only illustrates how beta carotene is turned into all-trans-retinoic acid but also how 13-cis-retinoic acid is turned into all-transretinoic acid.

http://pharmrev.aspetjournals.org/cgi/cont...ull/50/2/315/F5

Accutane is just mega dosing on 13-cis retinoic acid. This is the exact same logic.

Now i do not see why beta carotene couldnt do the same thing with perhaps minimal side effects. the problem is you would have to get it from natural sources because ive read that for some reason beta carotene supplements are not absorbed by the intestine so you have to get it from real foods. and you would have to get alot of it.

What do you all think?

Obviously this is still an unproven theory but it seems pretty solid.but i still plan on looking into why this wouldnt work.while simultaneously seeing if it helps.

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So will it work the same if you apply topical retinoids like Retin-A? Although I still prefer treating it internally, but I'm just curious what topical retinoid can do.

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So will it work the same if you apply topical retinoids like Retin-A? Although I still prefer treating it internally, but I'm just curious what topical retinoid can do.

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Accutane is just mega dosing on 13-cis retinoic acid. This is the exact same logic.

Now i do not see why beta carotene couldnt do the same thing with perhaps minimal side effects. the problem is you would have to get it from natural sources because ive read that for some reason beta carotene supplements are not absorbed by the intestine so you have to get it from real foods. and you would have to get alot of it.

What do you all think?

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Accutane is just mega dosing on 13-cis retinoic acid. This is the exact same logic.

Now i do not see why beta carotene couldnt do the same thing with perhaps minimal side effects. the problem is you would have to get it from natural sources because ive read that for some reason beta carotene supplements are not absorbed by the intestine so you have to get it from real foods. and you would have to get alot of it.

What do you all think?

I understood the conversion of beta carotene to be much less efficient, is that not true?

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Sorry, i should have explained more. I'll put it another way - you are hypothesizing that you can create a similar effect as isotretinoin via dietary beta-carotene, yes? But if the body regulates the conversion of beta carotene, and the problem is a faulty enzyme breaking it down too soon, how are you ever going to get ahead of the game using beta carotene? I mean, i think you are onto something that the fundamental issue here may be faulty Vitamin A metabolism, but how do you know that the body isn't already making as much as it is inclined to from the precursors? Will more precursors necessarily lead to more retinoic acid in the skin? Seems like you would have to overwhelm the enzyme production somehow the way a course of isotretinoin might hypothetically do. You see what i'm saying?

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Will you still get the orange skin effect eventhough you are taking beta-carotene in RDA and not over-dosing on it?

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Sorry, i should have explained more. I'll put it another way - you are hypothesizing that you can create a similar effect as isotretinoin via dietary beta-carotene, yes? But if the body regulates the conversion of beta carotene, and the problem is a faulty enzyme breaking it down too soon, how are you ever going to get ahead of the game using beta carotene? I mean, i think you are onto something that the fundamental issue here may be faulty Vitamin A metabolism, but how do you know that the body isn't already making as much as it is inclined to from the precursors? Will more precursors necessarily lead to more retinoic acid in the skin? Seems like you would have to overwhelm the enzyme production somehow the way a course of isotretinoin might hypothetically do. You see what i'm saying?

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According to certain studies the genetic cause for acne is an over active enzyme specifically in the skin that breaks down retinoic acid faster then it can be made, so then my theory is to create more in the cell via the beta carotene pathway to create a surplus and catch up with the rate it is being broken down.

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i currently have two threads going in the acne research section and this reply is kind of related to both in a way or demonstrates a relation between retinoic acid and omega 6 fatty acids.

1: Biochem Biophys Res Commun. 1987 Aug 31;147(1):25-30. Links

Interference of retinoic acid binding to its binding protein by omega-6 fatty acids.Sani BP, Allen RD, Moorer CM, McGee BW.

Cellular retinoic acid-binding protein (CRABP) is the putative mediator of the biological effects of retinoic acid in the control of epithelial differentiation and tumorigenesis. Omega-6 fatty acids such as linoleic acid and arachidonic acid, precursors of prostaglandin synthesis, caused inhibition of retinoic acid binding to CRABP. These fatty acids, however, possessed lower affinity than retinoic acid for the binding protein. Omega-3 fatty acids, such as eicosapentaenoic acid and docosohexaenoic acid, did not cause such inhibition in the binding of retinoic acid. Whereas retinoic acid was a potent modulator of differentiation of F9 embryonal carcinoma cells, neither omega-3 nor omega-6 fatty acids showed any significant differentiation potential. Competition by omega-6 fatty acids with retinoic acid for CRABP may neutralize the binding protein-mediated biological functions of retinoic acid, and could thereby enhance tumor production.

hmm this study was a complete and good surprise to me!!

so perhaps retinoic acid binding protein is also a factor in the pathogenesis of acne.

i do remember something cordain said as an argument for the paleo diet something to the effect of constant insulin surges can also lower retinoic acid binding protien. which is one reason simple sugars are bad for acne not to mention igf-1 tends to make acne worse.

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Hey AutonomousOne, can you pls elaborate the study some more because I really cant understand it. (sorry, LOL!) So is Omega-6 a good thing or a bad thing? What about GLA?

Thanks and keep it up! :)

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Hey AutonomousOne, can you pls elaborate the study some more because I really cant understand it. (sorry, LOL!) So is Omega-6 a good thing or a bad thing? What about GLA?

Thanks and keep it up! :)

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i do remember something cordain said as an argument for the paleo diet something to the effect of constant insulin surges can also lower retinoic acid binding protien. which is one reason simple sugars are bad for acne not to mention igf-1 tends to make acne worse.

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When I was in university, I took a lot of beta carotene to clear up my acne. It sure did. I never took enough to make my skin orange. But I don't recall how much I took. So I guess that wasn't much help. :P:)

Cam >B)

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This research/researchers:

http://www.ncbi.nlm.nih.gov/sites/entrez?D...Pubmed_RVDocSum

suggests that people who develop acne have significantly below normal vitamin A blood levels when they are diagnosed, and the severity of acne is correlated with the degree of deficiency.

So maybe a long-term subclinical dietary deficiency of beta carotene/vitamin A causes acne?

If so, perhaps that's what accutane does, it tops up the missing vitamin A, doses your skin so that the skin catches up with its vitamin A deficit and triggers differentiation in the pores and stops them blocking.

The problem is that the research on accutane shows that it's a particular total dose that resolves acne, and it's quite high dose (a long way above the normal physiological levels). So simply correcting your vitamin A/beta carotene deficiency could take quite a while to fix it; but presumably your skin would catch up on what it has missed eventually, and safely.

And that would explain why nobody made the connection before- correcting beta carotene levels wouldn't do much in the month or two that trials usually run for.

(Actually from what I've read it's not only beta carotene, it's fat, vitamin C, E and protein, and zinc- a deficiency of any of those significantly lowers your blood vitamin A levels, and presumably some people will have a disease that stops them absorbing vitamin A well, rather than simply a dietary deficiency).

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wow!! someone resurrected this thread.

nice study.

just for the record when i was trying this beta carotene over load thing, i would take fish oil pills(fat) with my carrot juice to make sure i absorbed every bit of beta carotene, well i only did this for three months but i for the effort i put in i didnt get much out of it.

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