On page 5:

QUOTE

Jeremy et al23 investigated the initiating events for

acne lesions, and found that immune changes and

inflammatory responses occur before hyperproliferation

of keratinocytes, with a pattern similar to a

type IV delayed hypersensitivity response. The

immune response is led by CD41 lymphocytes and

macrophages.23 These researchers hypothesize that

the subsequent production of cytokines activates

local endothelial cells, up-regulating inflammatory

vascular markers (E-selectin, vascular cell adhesion

molecule-1 [VCAM-1], intercellular adhesion

molecule-1 [iCAM-1], and human leukocyte antigen-

DR [HLA-DR]) in the vasculature around the

pilosebaceous follicle.23 They further have postulated

that the entire process is initiated by interleukin

(IL)-1a up-regulation in response to a relative linoleic

acid deficiency caused by excess sebum and perturbation

of barrier function within the follicle.23

Thanks for this information - but what does the second post mean? Didn't really get that.

QUOTE (lllhhk @ Jun 18 2011, 08:03 PM)

Thanks for this information - but what does the second post mean? Didn't really get that.

It says a couple of things pertinent to me. They were looking for the initiating events for the formation of acne lesions. And thus, at hyperkeratinization. And they found that there were inflammatory response and immune system response activity occur before the hyperproliferation of skin cells occur.

And in my Good Things thread under the Hyperkeratinization, Inflammation and the Food intolerance and Allergy sections, I have links to many studies showing that chronic inflammation from immune response or inflammatory diet habits, stress, lack of sleep, general poor lifestyle habits or whatever source, cause the improper cell differentiation, aptosis and desquamation that is at the root of what they call the condition hyperproliferation and hyperkeratinization.

What it means is that inflammation causes cells to be malformed, turnover at a rapid pace, yet not die at the proper rate becoming rough and sticky so that they do not exfoliate freely without clogging pores like they do in most people. And this tendency is genetically influenced.

Most of the rest of the paragraph are about the various things that go on in response to inflammation.

That paragraph also mentions a deficiency in linoleic acid and in my Good Things thread under Sebum, I have links to studies and info on this. It affects the quality of sebum and makes the difference between sebum that's sticky adding to the problem of pores not exfoliating freely and makes you look greasy, and sebum that makes your skin glow.

Here's another, also from 2009, about 'new' advances. Note all the talk about cell differentiation, proliferation, keratinocytes, etc. And especially nutrition, high glycemic meal habits and milk.

QUOTE

Department of Dermatology, Mie Universtity Graduate School of Medicine, Tsu, Mie, Japan. kuroichi@clin.medic.mie-u.ac.jp

(63view , 1users)

Interest in sebaceous gland physiology and its diseases is rapidly increasing. We provide a summarized update of the current knowledge of the pathobiology of acne vulgaris and new treatment concepts that have emerged in the last 3 years (2005-2008). We have tried to answer questions arising from the exploration of sebaceous gland biology, hormonal factors, hyperkeratinization, role of bacteria, sebum, nutrition, cytokines and toll-like receptors (TLRs). Sebaceous glands play an important role as active participants in the innate immunity of the skin. They produce neuropeptides, excrete antimicrobial peptides and exhibit characteristics of stem cells. Androgens affect sebocytes and infundibular keratinocytes in a complex manner influencing cellular differentiation, proliferation, lipogenesis and comedogenesis. Retention hyperkeratosis in closed comedones and inflammatory papules is attributable to a disorder of terminal keratinocyte differentiation. Propionibacterium acnes, by acting on TLR-2, may stimulate the secretion of cytokines, such as interleukin (IL)-6 and IL-8 by follicular keratinocytes and IL-8 and -12 in macrophages, giving rise to inflammation. Certain P. acnes species may induce an immunological reaction by stimulating the production of sebocyte and keratinocyte antimicrobial peptides, which play an important role in the innate immunity of the follicle. Qualitative changes of sebum lipids induce alteration of keratinocyte differentiation and induce IL-1 secretion, contributing to the development of follicular hyperkeratosis. High glycemic load food and milk may induce increased tissue levels of 5alpha-dihydrotestosterone. These new aspects of acne pathogenesis lead to the considerations of possible customized therapeutic regimens. Current research is expected to lead to innovative treatments in the near future.

PMID: 19555434 [PubMed - in process]

Another related study from same U:

http://www.ncbi.nlm.nih.gov/pubmed/19555434

Maybe derms read these reports, since they obviously don't look for/read current studies.

Here's what is hopefully a real advance:

While I have not seen the studies that found that the tendency towards hyperkeratinization is genetic, absolutely everything you find about hyperkeratinization and any condition that involves hyperkeratinization in the skin or elsewhere states that the tendency is genetic. It seems to be a given accepted by every researcher doing any research on any condition involving hyperkeratinization.

And here's a patent involving an enzyme encoded by gene UGCG that is involved in keratinocyte differentiation. They want to use it as a treatment for acne and any other condition that involves hyperkeratinization:

http://www.freshpatents.com/-dt20100204ptan20100028878.php

Apparently they want to inhibit the enzyme as a treatment/preventative. More than half way down there's a list of substances that they say do this.

And it mentions: 'Studies in vitro have shown that changes in the level of glucosylceramides stimulated keratinocyte proliferation (Uchida Y et al., J Invest Dermatol., 1994, 102: 594a; Marsh N L et al, J Clin Invest. 1995, 95:2903-2909). But when I search for that, I just find this patent

The full patent is viewble as a PDF.

More info on UGCG: http://en.wikipedia.org/wiki/UGCG

And here: http://www.genecards.org/cgi-bin/carddisp.pl?gene=UGCG Where it includes a chart with its genomic location.

And under Epigenetics it says:

'QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays for UGCG' I, of course, have no idea what that means, but epigenitics are things that we change in our life time due to environment and the things we do to ourselves that become part of our genetic makeup and can get passed down to our kids.

Good Things for Hyperkeratinization:

http://www.acne.org/messageboard/index.php...t&p=2580171

absolutely everything you find about hyperkeratinization and any condition that involves hyperkeratinization in the skin or elsewhere states that the tendency is genetic. It seems to be a given accepted by every researcher doing any research on any condition involving hyperkeratinization.

i hope that is not true, for the sake of science and the results that will ever be produced from its efforts. for the most part what ive seen is scientists are pretty good at remaining skeptical about any claims, but there are some exceptions.

absolutely everything you find about hyperkeratinization and any condition that involves hyperkeratinization in the skin or elsewhere states that the tendency is genetic. It seems to be a given accepted by every researcher doing any research on any condition involving hyperkeratinization.

 

 

i hope that is not true, for the sake of science and the results that will ever be produced from its efforts. for the most part what ive seen is scientists are pretty good at remaining skeptical about any claims, but there are some exceptions.

 

Well, I don't think they do it blindly. I think they do it based on genetic research I don't have access to or haven't yet found.

I have found a patent involving a gene identified as being involved in hyperkeritinization.

absolutely everything you find about hyperkeratinization and any condition that involves hyperkeratinization in the skin or elsewhere states that the tendency is genetic. It seems to be a given accepted by every researcher doing any research on any condition involving hyperkeratinization.

 

 

i hope that is not true, for the sake of science and the results that will ever be produced from its efforts. for the most part what ive seen is scientists are pretty good at remaining skeptical about any claims, but there are some exceptions.

 

 

Well, I don't think they do it blindly. I think they do it based on genetic research I don't have access to or haven't yet found.

 

I have found a patent involving a gene identified as being involved in hyperkeritinization.

 

oh ok, i see what you are saying then.

6-Sebum contains several matrix metalloproteinases (MMPs) which play important roles in the inflammatory process of acne. The levels of MMPs are significantly reduced in the acne lesions following treatment.

 

See, after the ZAG enzyme thread started focusing more on the enzymes involved in desquamation and less on the lectins that Cordain says inhibits them, I wondered what enzymes might be in normal sebum but my quick searches didn't produce any results. And this has been right here in this post all along.

Wikipedia definition.

Metalloproteinases (or metalloproteases) constitute a family of enzymes from the group of proteases, classified by the nature of the most prominent functional group in their active site. These are proteolytic enzymes whose catalytic mechanism involves a metal. Most metalloproteases are zinc-dependent, but some usecobalt.

So, they might just be talking about the ZAG, at least with the zind-dependent ones. But did Cordain ever tell us that ZAG was found in your sebum?

This is a better wikipedia article on the metalloproteinase matrix. Doesn't specifically mention the ZAG enzyme. A little bit about cell differentiation. And a bit about a cysteine switch. Cysteine is a sulfur containing amino acid and we hopefully all know by now how beneficial sulfur is, in the diet and topically.

Report focusing on the role of skin in the endocrine system and the affects of hormones on skin. Hormones such as IGF1, Vitamin D, thyroid hormones. And the sex hormones everyone thinks of when talking about acne:

http://hormones.gr/preview.php?c_id=49

-----

Also. numerous things deficient in acne prone skin:

Researchers have found that there are fewer lamellar granules in the Stratum Granulosum of acneic skin. As the lamellar granules contain the desquamation of enzymes and lipids that comprise the barrier layer in the intercellular spaces, this could account for the accumulation of cells in the follicle canal. Likewise, acneic skin is more permeable around the sebaceous gland and follicle, which may lead to leakage and inflammation into surrounding tissues. Studies have shown that linoleic acid, an essential fatty acid that is a component of the barrier lipid layer, is indeed deficient in acneic clients.

http://www.dermalinstitute.com/uk/library/19_article_What_is_Acne_.html

Perhaps it's a typo where it says 'desquamation of enzymes'. As opposed to 'desquamation enzymes.' Such as the ZAG enzyme, perhaps? None of our research and discussion of ZAG mentioned lamellar granules so perhaps these are yet more enzymes involved in separating skin cells so the exfoliate normally, i.e. desquamation. The article doesn't cite any references. Anyway, it's something new to search for.

Things that are different in acne prone skin:

-Deficiency in linoleic acid

-Fewer llamelar granulars that contain the desquammation enzymes and lipids

-More permeable around sebaceous glands and follicles

-There are more estrogen receptors in skin of the acne prone, especially in males. http://www.ncbi.nlm....pt=AbstractPlus And this one which also suggests that the number of androgen receptors in skin play a role in acne prone people with normal serum levels http://www.ncbi.nlm..../pubmed/6448587

-More of the enzymes that convert androgens and estrogen

-Deficient in retinoids, possible due to mutations in CYP26AI gene that causes it to be metabolized too fast to be used. See post below

TBC

About llamelar granulars

In the stratum granulosum layer of the epidermis, lamellar bodies are secreted from keratinocytes, resulting in the formation of an impermeable, lipid-containing membrane that serves as a water barrier and is required for correct skin barrier function. These granules release components that are required for skin shedding (desquamation) in the uppermost epidermal layer, the stratum corneum.^[2] These components include lipids (eg. glucosylceramides), hydrolytic enzymes (eg.proteases, acid phosphatases, glucosidases, lipases) and proteins (eg. corneodesmosin).^[3] Lamellar granules have been observed to contain distinct aggregates of the secreted components glucosylceramide, cathepsin D, KLK7, KLK8 and corneodesmosin. Transportation of molecules via lamellar granules is thought to prevent enzymes from interacting with their relevant substrates or inhibitors prior to secretion.^[3]

http://en.wikipedia....amellar_granule need to explore the references

New term of the day -

More Acne Vocabulary

Desquamation - the natural elimination of cells from the SC

apoptosis - programmed cell death.

desmosomes -

Retention Hyperkeratosis - rapid build up of cells in the follicles and the subsequent inability of the body to slough off those skin cells thereby creating a tough, glue-like substance leading to follicular blockage. Studies have found that individuals suffering from acne lack the necessary enzymes to break down the cellular glue that leads to the blockage. Since the follicle is blocked it provides the perfect non-oxygenated environment for P Acnes bacteria

Melatonin's role in normal cellular proliferation and differentiation.

http://www.ncbi.nlm....les/PMC1317110/

Because melatonin receptors are expressed in skin cells, these have the potential to mediate phenotypic actions on cellular proliferation and differentiation.

and further down

Melatonin inhibits both apoptosis of keratinocytes incubated in serum-free media and proliferation of keratinocytes cultured in medium supplemented with serum.

In addition to it's role in sleep and a natural circadian cycle which affects everything. Carb metabolism, hormones, stress, etc. Melatonin also protects from sun damage

----------------

VIP was found to stimulate proliferation of keratinocytes in the presence of lethally treated 3T3 fibroblast feeder cells and EGF, whereas substance P and CGRP were ineffective⁶⁷. VIP stimulated adenylate cyclase activity in membranes obtained from cultured keratinocytes, indicating an involvement of cAMP as second messenger in this reaction. VIP and several inflammatory cytokines (Th-1 and 2) from mast cells and nerve endings are capable of inducing stem cell factor production from epidermal keratinocytes, a mechanism that could be involved in atopic dermatitis⁶⁸.

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!!

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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

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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.

http://www.ncbi.nlm....st_uids=9557256

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.nih.gov/pubmed/15675964?dopt=Abstrac t" class="bbc_url" title="External link" rel="nofollow external"> http://www.ncbi.nlm....4?dopt=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.nih.gov/pubmed/1596469 2" class="bbc_url" title="External link" rel="nofollow external"> http://www.ncbi.nlm....pubmed/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.nih.gov/pubmed/16778795?dopt=Abstrac t" class="bbc_url" title="External link" rel="nofollow external"> http://www.ncbi.nlm....5?dopt=Abstract</a>concludes<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.nih.gov/pubmed/3182850?dopt=Abstrac t" class="bbc_url" title="External link" rel="nofollow external"> http://www.ncbi.nlm....0?dopt=Abstract</a>

Expression and function of cytochrome p450-dependent enzymes in human skin cells.

<a href=" http://www.ncbi.nlm.nih.gov/pubmed/1878194 7" class="bbc_url" title="External link" rel="nofollow external"> http://www.ncbi.nlm....pubmed/18781947</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.com/jid/journal/v123/n3/full/5602457a.htm l" class="bbc_url" title="External link" rel="nofollow external"> http://www.nature.co...l/5602457a.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.com/jid/journal/v123/n3/full/5602457a.html#tbl 1" 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.com/jid/journal/v123/n3/full/5602457a.html#bib8 1" class="bbc_url" title="External link" rel="nofollow external">VanWauwe and Janssen, 1989</a>; <a href=" http://www.nature.com/jid/journal/v123/n3/full/5602457a.html#bib2 1" 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.com/jid/journal/v123/n3/full/5602457a.html#bib3 9" 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.com/medical-notes/o-g-and-paeds/17/39/25 1" class="bbc_url" title="External link" rel="nofollow external"> http://www.fastbleep...paeds/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.nih.gov/pubmed/2211077 3" class="bbc_url" title="External link" rel="nofollow external"> http://www.ncbi.nlm....pubmed/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.org/content/22/2/538.full#B3 6" class="bbc_url" title="External link" rel="nofollow external"><img src=" http://www.fasebj.org/icons/ref-arrow.gi f" 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.org/content/22/2/538.full#B3 8" class="bbc_url" title="External link" rel="nofollow external"><img src=" http://www.fasebj.org/icons/ref-arrow.gi f" alt="Posted Image" class="bbc_img"></a><span style="color: #403838"> 39</span><a href=" http://www.fasebj.org/content/22/2/538.full#B3 9" class="bbc_url" title="External link" rel="nofollow external"><img src=" http://www.fasebj.org/icons/ref-arrow.gi f" alt="Posted Image" class="bbc_img"></a><span style="color: #403838"> 40</span><a href=" http://www.fasebj.org/content/22/2/538.full#B4 0" class="bbc_url" title="External link" rel="nofollow external"><img src=" http://www.fasebj.org/icons/ref-arrow.gi f" alt="Posted Image" class="bbc_img"></a><span style="color: #403838"> 41)</span><a href=" http://www.fasebj.org/content/22/2/538.full#B4 1" class="bbc_url" title="External link" rel="nofollow external"><img src=" http://www.fasebj.org/icons/ref-arrow.gi f" 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.org/content/22/2/538.full#F 6" class="bbc_url" title="External link" rel="nofollow external"><img src=" http://www.fasebj.org/icons/ref-arrow.gi f" 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.org/content/22/2/538.ful l" class="bbc_url" title="External link" rel="nofollow external"> http://www.fasebj.or...t/22/2/538.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.nih.gov/pubmed/1880365 8" class="bbc_url" title="External link" rel="nofollow external"> http://www.ncbi.nlm....pubmed/18803658</a>

Carotenoids and other phytonutrients protect from photodamage

<a href=" http://www.ncbi.nlm.nih.gov/pubmed/2225406 2" class="bbc_url" title="External link" rel="nofollow external"> http://www.ncbi.nlm....pubmed/22254062</a><p></p>

.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.

Deficiency in linoleic acid (not to be confused with linolenic acid) I believe was just in the sebum gland itself, not an overall dietary deficency. (Ive taken hemp oil, evning primrose both rich in linoleic acid with no results either than a greasy pillow when i wake up...yuck!)

I wonder, if the immune response (and ultimate inflammation) preceeds everything else in acne...then wouldnt it make sence to 'modulate your immune system'?

Leaky gut comes to mind, with a constant 'primimg' of and immune response to food.

High fiber, no dairy, probiotics and L-Glutamine are the most common suggestions for leaky gut.

Also, vitamin D. I have a gene that makes me gentically prone to LOW vitamin D levels (I have type 1 diabetes, research published last year identified a shared gene in type 1 diabetes, MS, and a few other autoimmune diseases) I supplememnt with 2000iu daily, a bit more in the winter.

I wonder, if the immune response (and ultimate inflammation) preceeds everything else in acne...then wouldnt it make sence to 'modulate your immune system'?

 

I've seen several studies, or perhaps articles on the same few studies, that says they found that inflammation causes the malformed cells/impaired desquamation. The report in the first post says that and there are links to studies in my Good Things thread under the Inflammation and Hyperkeratinization sections. And possibly the immune system section.

I believe the inflammation can come from any number of sources besides immune response, such as the damaged digestive tract so many people think we all have, although the digestive tract is an important part of the immune system as well. Also, there are other inflammatory responses besides antibodies.

But yes, you should always try to keep a good immune system. You don't want to be a victim of our terrible 'health' care system and food industry. http://www.acne.org/messageboard/index.php/topic/230714-good-things-for-the-many-factors-that-lead-to-acne/page__view__findpost__p__2585034

About the sebum making us age faster I think that would be true!

Our cells basically age because of dividing and reproducing. The more it does that the older it gets.

Yesterday I just noticed that my skin would shed around the area with the most oil. So that could mean sebum does increase reproduction or just lessens the life span of them.

Another genetic thing:

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

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.

 

A gene involved in our ability to metabolize retinoids in our skin.

 

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.

 

This is an enzyme that could break down retinoic acid quicker than it can be used. Enzymes are how genes perform their functions, FYI. There's usually an enzyme for every gene. That's why it might look like enzyme and gene seem to be use interchangeably.

In a patent request for a resveraterol topical treatment for acne and other skin conditions:

http://www.freepatentsonline.com/y2001/0056071.html

Acne

[0025] A randomized, double blind study was carried out in order to evaluate the effectiveness of topical administration of resveratrol in the treatment of acne vulgaris. Patients (n=30) of 15 to 19 years were all suffering from II or III degree acne (according to Pillsbury's classification), with multiple inflammatory lesions (20 to 62) and a number of comedos (28 to 120) on face and forehead. Only subjects who had received no systemic treatment with antibiotics for at least 4 weeks and had used no topical medicaments for 2 weeks before treatment were selected. During treatment with resveratrol, no further topical treatment was allowed. The effectiveness of the therapy was evaluated by comparing the conditions of the lesions before and after the treatment, according to an arbitrary score of 0 to 5 (0=worsening; 1=no changes; 2=slight improvement; 3=modest improvement; 4=good improvement; 5=excellent improvement).

[0026] Treatment

[0027] Treatment consisted of daily topical administrations of resveratrol (1% cream) or of the carrier only, for 10 weeks in 30 patients suffering from acne vulgaris. The evaluated parameters were: number of acne lesions and comedos, erythema, seborrhoic skin and skin scaling.

[0028] Results

[0029] Patients treated with resveratrol showed neither systemic nor topical side effects. A significant reduction of erythema, number of acne lesions, comedos and, above all, scaling, was observed in treated subjects (96%), compared with control subjects (2%). More particularly, the effectiveness of the treatment in 95% of cases proved to be due to the reduction of follicle hyperkeratosis, which is an important factor in the formation of comedos since it causes thickening of the follicle wall with sebum retention.

 

Resveraterol discussion thread: http://www.acne.org/messageboard/index.php/topic/165897-resveratrol/

Resveratrol is a potent 5 lipoxygenase inhibitor. 5 lipoyxgenase converts arachinodic acid into pro-inflammatory leukotrines. According to the studies posted by autonomous, these leukotrines can stimulate the sebaceous glands. Arachinodic downregulates PPARs, which affect rxr receptors, just like how accutane works!

 

In additionm, resveratrol is a CYP1A1 enzyme inhibior. CYP1A1 is an ezyme that encourages the breakdown of retinoic acid which maybe be the reason why the cells in our skins begin to disfunction, resulting in hyperkeratinization.

See the above post on the CYP1A1 gene affecting acne prone skin.

Here's someone else's list of things different in acne prone skin. Except that we don't necessarily all have all of these things going on.:

• A higher level of free testosterone. The levels of free testosterone in males is 9 to 30 ng/dL, and in females it's 0.3 to 1.9 ng/dL
• Increased level of the enzyme 5-alpha reductase. This converts the less potent androgens, such as testosterone and androsterone, into dihydrotestosterone (DHT), which has a greater effect on sebum production
• Adrenocorticotrophic hormone (ACTH) from the pituitary gland influences the adrenal gland, which produces the androgenic steroid dehydroepiandrosterone (DHEA)
• Higher levels of dehydroepiandrosterone (DHEA) are found in the sebaceous glands. This in turn is converted by 5-alpha reductase into DHT
• Dehydroepiandrosterone sulfate (DHEAS) is significantly and specifically associated with the initiation of acne in young girls
• Follicular hyperkeratosis or abnormal follicular keratosis
• Increased sebum production
• Bacterial infection by Propionibacterium acnes. Although P. acnes is a normal inhabitant of the skin, its levels are higher in patients with acne
• Sebum from patients with acne is deficient in linoleic acid
• Higher levels of insulin-like growth factor 1 (IGF-I)
• Acne-prone skin has been shown to be insulin resistant
• Adrenal hyperplasia
• A positive association has been found between acne and total milk intake. Probably because of the various hormones present
• d-Chiro-, myo-inositol and inositol increases the action of insulin, which decreases serum androgen concentrations, blood pressure, and plasma triglyceride concentrations.

Natural remedies, with special reference to progesterone as a potentially effective pimple and acne cream...

• Progesterone inhibits 5 alpha-reductase activity at high doses, studies show it has a local anti-androgenic action
• Progesterone also inhibits the production of androgens within the body
• Progesterone reverses follicular keratosis
• Progesterone causes a significant reduction in sebum excretion in women
• Zinc is a potent inhibitor of 5 alpha-reductase activity
• Vitamin B6 potentiates the inhibitory effect of zinc
• d-Chiro-inositol, myo-inositol and inositol help increase the action of insulin
• Azelaic acid is also a potent inhibitor of 5 alpha-reductase Type 1. It is a natural plant acid found in wheat, barley and rye. A 20% topical cream has been found to be effective against mild to moderate acne by reducing the activity of the bacteria Propionibacterium acnes and Staphylococcus epidermidis
• Both acne and insulin sensitivity improve after a low-glycaemic-load diet
• Phototherapy has been successful in treating acne, in particular intense violet light. When red visible light is added it works even better
• Supplementing with vitamin D is a cheaper option than phototherapy
• Vitamin D is essential for health, including skin health. Have a blood test done to check the level. The test should only be done for 25-hydroxyvitamin D, also called calcidiol
• 30-50% of people have a Vitamin D deficiency, particularly those living in climates with little sun, living above 32 degrees north or south of the equator, work indoors and spend little time in the sun. Levels should be between 50-100ng/mL or 124.80-249.60nmol/L. A deficiency is less than 25ng/L or 62.4nmol/L. For more information please see here

Read more: http://www.progester...l#ixzz1sJq5Fv2Y
Under Creative Commons License: Attributio

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They also have some interesting info on causes of estrogen dominance/low progesterone such as stress, vitamin D deficciency, large meals (due to the increased metabolic clearance rate of progesterone) and of course estrogens in food, plastics, water, etc.
Read more: http://www.progester...l#ixzz1sJrBgQjz

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Here's a study on the effects of a meal on circulating progesterone levels: http://www.ncbi.nlm..../pubmed/2778041
They started with women with fasting women with a steady amount of circulating Progesterone due to supplementation by infusion. Then found their P levels dropped while cortisol rose after a meal? They don't discuss what happens with the progesterone so I'm not sure if this is a 'good' thing or a 'bad' thing. The cortisol is 'bad.' And this article on causes of estrogen dominance mentions the 'metabolic clearing of progesterone after a large meal. So I'm thinking this is undesirable. So Is this perhaps an example of the benefits of Intermittent fasting?

Not sure if you stated this already, but do you think GMOs have anything to do with this? I have heard GMOs doing terrible stuff, but not sure if it could mess with genetics.

^No, not so far. But I have read that it's usually lectins that they are switching around when modifying something. And lectins are a big culprit in intestinal damage, allergy, and some may inhibit enzymes involved in normal cell desquammation.

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A paper some people might be interested in:

The Role of Innate Immunity in the Pathogenesis of Acne
http://www.cunliffe-awards.de/pdfs/publikation_koreck-pivarci.pdf

The pdf is formatted to impede copying and pasting.

On the subject of progesterone, vitamin E apparently has anti-estrogenic properties and essentially boosts progesterone. I wanted to get some vitamin E oil today since it's hard to get adequate amounts from food, but a lot of them had things like soybean oil and wheat germ oil in them. Do you know if those can cause reactions if applied topically, alternativista?

Complete journal article on a study that shows that inflammatory events initiate acne formation processes.

'

Inflammatory Events Are Involved in Acne Lesion Initiation'

http://www.nature.com/jid/journal/v121/n1/full/5601829a.html

Clinical implications of lipid peroxidation in acne vulgaris: old wine in new bottles.

 

 

Bowe WP, Logan AC.

 

 

 

 

Source

Department of Dermatology, State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA. [email protected]

 

 

 

 

Abstract

Acne vulgaris is a common dermatological disorder, one that is frequently associated with depression, anxiety and other psychological sequelae. In recent years there has been an increasing focus on the extent to which oxidative stress is involved in the pathophysiology of acne. Emerging studies have shown that patients with acne are under increased cutaneous and systemic oxidative stress. Indeed, there are indications that lipid peroxidation itself is a match that lights an inflammatory cascade in acne. The notion that lipid peroxidation is a 'starter gun' in acne is not a new one; here we review the nearly 50-year-old lipid peroxidation theory and provide a historical perspective to the contemporary investigations and clinical implications.In addition, we present a novel hypothesis in which lipid peroxidation may be priming an increased susceptibility to co-morbid depression and anxiety in those with acne. The emerging research on the systemic burden of oxidative stress in acne sheds further light on the brain-skin axis. The recent findings also suggest potential avenues of approach for the treatment of acne via specific nutrients, dietary modifications, oral and topical interventions.

 

 

 

Interesting article that sites a lot of theories and research that are 50 years old. Such as that oxidative breakdown of squalene and other skin lipids may not merely be a consequence of the acne process, but be directly 'acnegenic to the skin'. and sites research that found success with the topical use of antioxidants E, A and C to support normal keratinization. Full article available: http://www.ncbi.nlm....32/?tool=pubmed which includes the following:

It has been discovered that subclinical inflammatory events are occurring in acne-prone skin even prior to hyperproliferative and abnormal differentiation events [11,12]. The reason for elevated pro-inflammatory factors, such as interleukin-1 (IL-1), around the clinically normal pilosebaceous follicles of acne patients remains unknown. At this point it simply highlights that the release of inflammatory chemicals is indeed one of the earliest events to occur in the acne process. Furthermore, oxidative stress within the pilosebaceous unit alters the environment from one that is unsuitable to harbor anaerobic bacteria to one that is perfectly suited for the colonization of such species [13]. P. acnes, once thought to be the initiating factor of inflammatory acne, might never make the pilosebaceous unit its home were it not for this initial inflammatory insult to the sebum. Oxidation of sebum alters oxygen tension in the follicle, resulting in the micro-aerophilic environment required for P. acnes to survive. Apparently, inflammation and oxidative stress might set the stage for all subsequent pathogenic factors leading to acne.

Note that linoleic acid, something that acne and other skin problem-prone people are deficient in, inhibits IL-1 amongst it's other anti-inflammatory qualities.

Zinc and IGF-1-

Propionibacterium acnes activates the IGF-1/IGF-1R system in the epidermis and induces keratinocyte proliferation.

 

 

 

Isard O, Knol AC, Aries MF, Nguyen JM, Khammari A, Castex-Rizzi N, Dreno B.

 

 

 

 

Source

INSERM U892, 9 Quai Moncousu, Nantes, France.

 

 

 

 

Abstract

Propionibacterium acnes has a major role in the development of acne lesions. IGF-1 stimulates the proliferation of keratinocytes via an activation of the IGF-1 receptor (IGF-1R). Zinc has been proven to work efficiently against inflammatory acne and to modulate the IGF-1 system. Our objectives were to study the modulation of IGF-1 and IGF-1R expression by P. acnes extracts and to determine their modulation by zinc gluconate. In vivo, we analyzed biopsies of acne lesions and healthy skin, and in vitro we used skin explants incubated with two P. acnes extracts--membrane fraction (MF) and cytosolic proteins--with or without zinc. IGF-1 and IGF-1R expression was evaluated using immunohistochemistry, and the IGF-1 production in supernatants was measured by ELISA. Then, IGF-1 and IGF-1R mRNA levels were analyzed using quantitative PCR on normal human epidermal keratinocytes (NHEKs). IGF-1 and IGF-1R were overexpressed in acne lesions. MF increased IGF-1 and IGF-1R expression in the epidermis of explants and was associated with an overexpression of both Ki-67 and filaggrin. Zinc had the effect of downregulating IGF-1 and IGF-1R levels. These observations were confirmed at the mRNA level for IGF-1R in NHEKs. These results demonstrate that P. acnes can induce the formation of comedones by stimulating the IGF/IGF-1R system. Moreover, zinc downregulates this pathway.

 

 

 

http://www.ncbi.nlm....pubmed/20927124