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In Topic: 'recent' Advances In Acne Pathogenesis Information

21 October 2014 - 08:20 AM

Beta carotene, UV exposure and Retinoic Acid

Trying to follow up on a theory by autonomousone

acne may be a genetic defect in vitamin a metabolism particularly with the pathway that creates retinoic acid in the skin. iv</strong>e read studies that suggest retinoic acid could be rendered inactive in our bodies so we may have ultra low levels of it, sending our skin and sebum cells into chaos.

BETA CAROTENE is derived from plants only and enters the body as ~60% beta carotene and 40 % retinal . the body can then turn retinal into retinol as needed and the body can store large amounts of beta carotene with no known overdose. So the true source of retinol is beta carotene ...
one other interesting fact to consider is that our skin stores a lot of our beta carotene intake thats why eating too many carrots can turn your skin orange. i also find it interesting that acne mainly occurs on the face and the back and these are places that are otherwise exposed to the sun when walking outside, <strong>and ive read a study that proves uv rays cause beta carotene to stimulate retinoic acid production</strong>. Interestng thoughts hey!!


We are lacking/have too much of/have a mutation in the CYP26AI enzyme/gene in involved in the metabolism of retinoic acid in our skin?? And UV involvement in stimulating retinoic acid production could be one way many people's skin clears when they get more sun exposure


Polymorphisms in the human cytochrome P-450 1A1 gene (CYP1A1) as a factor for developing acne.
Paraskevaidis A, Drakoulis N, Roots I, Orfanos CE, Zouboulis CC.
Department of Dermatology, University Medical Center Benjamin Franklin, Free University of Berlin, Germany.

Cytochromes P-450 are a supergene family of enzymes involved in the metabolism of a wide range of endogenous and foreign compounds. The existing genetic variations of the distinct isozymes lead to interindividually different metabolic capacity. Since vitamin A, endogenous retinoids and their natural metabolites are morphogenic for the sebaceous gland, we investigated the polymorphisms of cytochrome P-450 1A1, as being one of the most active isozymes involved in their interconversion. From the known mutations, two were investigated; an additional cleavage site for MspI in the 3'-flanking region identified as a thymine-to-cytosine transition 1,194 bp downstream of exon 7 (m1) and an adenine-to-guanine transition at position 4889 in exon 7 (m2). We studied 96 acne patients for m1 and m2 mutations by restriction fragment length polymorphism and allele-specific polymerase chain reaction, respectively, and compared the results with 408 reference individuals. No statistically significant difference was found in the distribution of m2 alleles; the frequency was 3.13 and 3.06% of the alleles, respectively (odds ratio = 1.02, confidence limits 0.41-2.52, p = 0.96). In contrast,a trend to an overrepresentation of m1 alleles in acne patients was observed; allele frequency was 8.33 in the patients and 6.99% in the control subjects, respectively (odds ratio 1.21, 95% confidence limits 0.68-2.16, p = 0.52). As the m1 mutation might define a marker for alterations on regulatory sites, the biological efficacy of natural retinoids could be greatly impaired by their rapid metabolism to inactive compounds. The resulting deficit of active natural retinoids may lead to abnormal sebocyte differentiation and hyperkeratinization of the follicular canal implicating the development of acne in some patients.


Dermatology. 1998;196(1):171-5. Related Articles, Links

Promotes keratinocyte differentiation and apoptosis:
"Combination of betaC-promoted keratinocyte differentiation with the cellular "UV response" caused synergistic induction of cell cycle arrest and apoptosis." <a href="http://www.ncbi.nlm....?dopt=Abstract" class="bbc_url" title="External link" rel="nofollow external">http://www.ncbi.nlm....pt=Abstract</a>

"UV-induced cell death by apoptosis is considered to be a natural protective mechanism that removes damaged keratinocytes and circumvents the risk of malignant transformation." <a href="http://www.ncbi.nlm....ubmed/15964692" class="bbc_url" title="External link" rel="nofollow external">http://www.ncbi.nlm....ed/15964692</a>

About the skin's ability to metabolize retinoic acid from beta carotene:

Skin retinoid concentrations are modulated by CYP26AI expression restricted to basal keratinocytes in normal human skin and differentiated 3D skin models.
<a href="http://www.ncbi.nlm....?dopt=Abstract" class="bbc_url" title="External link" rel="nofollow external">http://www.ncbi.nlm....des<em><strong> '

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 <strong>altered RA metabolism may be involved in the pathogenesis of acne

Biogenesis of retinoic acid from beta-carotene. Differences between the metabolism of beta-carotene and retinal.
<a href="http://www.ncbi.nlm....?dopt=Abstract" class="bbc_url" title="External link" rel="nofollow external">http://www.ncbi.nlm....pt=Abstract</a>

Expression and function of cytochrome p450-dependent enzymes in human skin cells.
<a href="http://www.ncbi.nlm....ubmed/18781947" class="bbc_url" title="External link" rel="nofollow external">http://www.ncbi.nlm....47</a></strong>

"human skin cells express various CYP enzymes, including </span></span></p><strong>CYP26AI which is responsible for the metabolism of retinoic acid in skin cells"

Good report with sources for research:
Cytochrome P450: A Target for Drug Development for Skin Diseases
;<a href="http://www.nature.co.../5602457a.html" class="bbc_url" title="External link" rel="nofollow external">http://www.nature.co...02457a.html</a>

The special interest for CYP enzymes in skin is evident by the fact that most, if not all, drugs used by the practicing dermatologist are either substrate or inducer, or inhibitor of this enzyme family (<a href="http://www.nature.co...457a.html#tbl1" class="bbc_url" title="External link" rel="nofollow external">Table I</a>. It is important to mention here that CYP enzymes act on many endogenous substrates including vitamin D and vitamin A, which are widely used in clinical practice for treating a variety of dermatological disorders....

Liarozole, which is an imidazole-containing compound, is known to inhibit the CYP-mediated metabolism of t-RA resulting in an increase of the retinoid in skin and plasma ( <a href="http://www.nature.co...57a.html#bib81" class="bbc_url" title="External link" rel="nofollow external">VanWauwe and Janssen, 1989</a>; <a href="http://www.nature.co...57a.html#bib21" class="bbc_url" title="External link" rel="nofollow external">Dockx <em>et al</em>, 1995</a></sup>

Cyp enzymes also affect vitamin D production:

Based on several studies, it is now clear that the active form of vitamin D and its analogs suppress growth and stimulate the terminal differentiation of keratinocytes ( <a href="http://www.nature.co...57a.html#bib39" class="bbc_url" title="External link" rel="nofollow external">Kira <em>et al</em>, 2003</a>
It is also known that in psoriatic lesions, epidermal keratinocytes exhibit hyper-proliferation and impaired differentiation triggered by inflammation. Therefore, it is quite reasonable to assume that vitamin D is effective on psoriasis.

From this on hirsutism and PCOS <a href="http://www.fastbleep...aeds/17/39/251" class="bbc_url" title="External link" rel="nofollow external">http://www.fastbleep...s/17/39/251</a>

Spironolactone: An aldosterone antagonist. Reduces Hitsutism through competitive inhibition of DHT, reduces CYP enzyme and increases peripheral aromatisation of testosterone and inhibition of skin 5 alpha reductase.

Vitamin A and its natural and synthetic metabolites ( retinoids) affect growth and differentiation of human skin and among the genes affected by retinoids in epidermis are keratin genes. <a href="http://www.ncbi.nlm....ubmed/22110773" class="bbc_url" title="External link" rel="nofollow external">http://www.ncbi.nlm....ed/22110773</a>

"Vitamin A and its natural and synthetic metabolites (retinoids) affect growth and differentiation of human skin and among the genes affected by retinoids in epidermis are keratin genes."</p>

Retinoids might also help by being anti-inflammatory: Inflammation resolved by retinoid X receptor-mediated inactivation of leukotriene signaling pathways (Such as by acting PPARs.)

"Leukotrienes are implicated in the pathogenesis of diverse, inflammation-driven diseases.... Retinoids affect numerous signaling pathways in human skin (36) <a href="http://www.fasebj.or...2/538.full#B36" class="bbc_url" title="External link" rel="nofollow external"><img src="http://www.fasebj.or.../ref-arrow.gif" alt="Posted Image" class="bbc_img"></a><span style="color: #403838"> .
Their antiinflammatory, prodifferentiating, and chemopreventative properties are efficacious toward diverse disorders including psoriasis, acne, ichthyosis, photoaging, cancer, emphysema, and bronchopulmonary dysplasia in newborns (38</span><a href="http://www.fasebj.or...2/538.full#B38" class="bbc_url" title="External link" rel="nofollow external"><img src="http://www.fasebj.or.../ref-arrow.gif" alt="Posted Image" class="bbc_img"></a><span style="color: #403838"> 39</span><a href="http://www.fasebj.or...2/538.full#B39" class="bbc_url" title="External link" rel="nofollow external"><img src="http://www.fasebj.or.../ref-arrow.gif" alt="Posted Image" class="bbc_img"></a><span style="color: #403838"> 40</span><a href="http://www.fasebj.or...2/538.full#B40" class="bbc_url" title="External link" rel="nofollow external"><img src="http://www.fasebj.or.../ref-arrow.gif" alt="Posted Image" class="bbc_img"></a><span style="color: #403838"> 41)</span><a href="http://www.fasebj.or...2/538.full#B41" class="bbc_url" title="External link" rel="nofollow external"><img src="http://www.fasebj.or.../ref-arrow.gif" alt="Posted Image" class="bbc_img"></a><span style="color: #403838"> . We present evidence that retinoids up-regulate a proresolving pathway in human epidermal keratinocytes by mechanisms involving RXR-mediated </span><em>CYP4F</em><span style="color: #403838">transcriptional activation (</span><strong>Fig. 6</strong><a href="http://www.fasebj.or.../2/538.full#F6" class="bbc_url" title="External link" rel="nofollow external"><img src="http://www.fasebj.or.../ref-arrow.gif" alt="Posted Image" class="bbc_img"></a><span style="color: #403838"> ). One result is increased epithelial capacity to metabolically inactivate leukotrienes produced by infiltrating neutrophils, thereby antagonizing LTB4 signaling and further neutrophil recruitment. This CYP4F-dependent pathway functions as a physiological stop signal for epithelial inflammation, facilitating the switch to tissue repair and wound healing. </span><span style="color: #403838">"&nbsp;&nbsp; There's talk of celiac disease near the end of the full text..</span>
<a href="http://www.fasebj.or.../22/2/538.full" class="bbc_url" title="External link" rel="nofollow external">http://www.fasebj.or.../2/538.full</a>

Caratenoids and how they protect us from UVA damage with a comparison of beta carotene, Astaxanthin, and canthaxanthin
<a href="http://www.ncbi.nlm....ubmed/18803658" class="bbc_url" title="External link" rel="nofollow external">http://www.ncbi.nlm....ed/18803658</a>

Carotenoids and other phytonutrients protect from photodamage
<a href="http://www.ncbi.nlm....ubmed/22254062" class="bbc_url" title="External link" rel="nofollow external">http://www.ncbi.nlm....4062</a><p></p>

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.

Cordain may have said something about insulin surges can also lowering retinoic acid binding protien. (along with other factors like sex hormone binding globulin.



It's has been awhile since I posted on this site but I wanted to report a partial success I had with Vitamin A. This theory about UV light definetly holds some truth. I noticed that after taking Vitamin A in the form of 10,000 IU of retinol (the animal source, not beta carotene) and exposing my face and body to the sun every other day for an adequate amount of time, I could manage my acne to an extent. Now this didn't "cure" or completely cure my condition but it helped tremendously. I must note that during this time I was eating very healthy and also consumed many sources of plant sourced Beta-carotene from spinach, carrots, sweet potatoes, butternut squash, etc. Although I suggest only using retinol at first (since it is already converted to the active Vitamin A form whereas the conversion rate of beta-carotene is very low) beta-carotene could have still played a factor since I know that beta carotene is deposited in the surface skin and acts as an fat soluble antioxidant, and an electron acceptor from the sun.


This further supports the evolutionary biology approach to acne. At my worst points, I experienced severe acne on my face, and tops of my back and chest, the areas on the body that would be exposed most to the sun when we lived primitively. I believe we evolved a higher density of retinoic acid receptors in these areas of the skin so that more sun light was needed to produce a normal amount of retinoic acid. Now, our traditional american diets are low in Vitamin A, and antioxidants/pigments (zeaxanthin, astaxanthin, lutein, beta-carotene, lycopene) and we are being told to avoid the sun at all cost. My theory is that the sun and its "harmful" UV's do NOT cause skin cancer, but our lack of internal protection allow us to be susceptible to cancer. Please don't quote me saying that vitamin a cures skin cancer, this is just a theory on acne and the skin. And again I must stress that acne is multifactorial and this is just on of the ways it can "get" you, not including omega 3:6 ratio, hormone imbalace, etc...

In Topic: Chicken breaks me out - What does it mean?

06 February 2014 - 03:40 PM

chicken fed soy based feed have higher tissue concentrations of arachidonic acid (and their eggs too), much higher in fact. Arachidonic Acid is a type of Omega-6 that is more inflammatory than Linoleic Acid, which is the more common Omega-6 fat. I also break out from excessive chicken and excessive egg intake. I can eat it occasionally without a problem though. It would be unwise to consume chicken as your only meat, go with grass fed beef or wild salmon.

In Topic: Cleared My Acne 90%, Here's How!

08 December 2013 - 01:51 PM


That's unfortunate :/

How about b5 and l-carnitine, do you think it does still help you?

Good luck anyway!

I completely forgot about b5. There are so many factors that I have since pinpointed so its hard to look far back and know what was or wasnt breaking me out. Maybe I will investigate the B5 & L-Carnitine combo again, but I'm trying to focus on a deeper, root cause.

In Topic: Cleared My Acne 90%, Here's How!

07 December 2013 - 01:03 PM

Hi just wanted to update since it has been so long. I still struggle with acne daily. While eliminating soy and flax has helped, I am not even close to clear. Fiber no longer affects my acne at all. It seemed at one point that I could control most of my acne by supplementing with both a soluble and an insoluble fiber. This is no longer the case. Juicing is also helpful but I cannot afford to do it. I also don't have the time in my day to do it. Also, I no longer own a juicer. Haha. 

In Topic: Autoimmune Paleo & Pufas

07 December 2013 - 01:00 PM

Just wanted to update quickly by saying that eliminating all PUFA's except for those in wild salmon eaten once every 2 days, and eating an autoimmmune paleo diet did not get me clear, or as clear as I was aiming for. I'm still uncertain how each food affects me. I know for certain that kale, broccoli, cabbage, soy, flax, and any vegetable oils will worsen my acne. I believe that eating too much sugar, dairy, and grains can worsen my acne, but the link is not as clear as goitrogens and soy/omega 6's for me. I also don't know at all if legumes, nuts, or nightshades break me out. I definetly feel that my acne is at its best when I eat something close to Autoimmune Paleo emphasizing on an elimination of PUFA's, but it is difficult to have energy when you are low carb. I think that some grain like rice, oats, and quinoa are okay to eat. My quest for clear skin is astronomically frustrating. I feel like I know so much about nutriition and the body but I am so far away from my particular solution. Any advice is helpful even if its on the fringes of science/health. Right now I am currently investigating hypothyroidism by increasing my carb intake and taking a dessicated porcine thyroid supplement multi-dosed throughout the day. I am also supplementing with Retinol or vitamin A from animal sources. There is no soybean oil in my supplement. I am leaning more and more to the fact that diet can't cure my acne. I am speaking only about my particular case. I have tried so many diets with small successes. Anti-candida, paleo, autoimmune paleo, wai, vegetarian, vegan etc... I think there is fundamentally something wrong in my body, like a genetic difference or a chronic condition that results in inflammation. WHAT IS IT!??!