Acne vulgaris, probiotics and the gut-brain-skin axis - back to the future?

Whitney P Bowe¹ and Alan C Logan²

¹Department of Dermatology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203, USA

²Integrative Care Centre of Toronto, 3600 Ellesmere Road, Unit 4, Toronto, ON M1C 4Y8, Canada

Corresponding author.

Whitney P Bowe: [email protected]; Alan C Logan: [email protected]

Received December 27, 2010; Accepted January 31, 2011.

Over 70 years have passed since dermatologists John H. Stokes and Donald M. Pillsbury first proposed a gastrointestinal mechanism for the overlap between depression, anxiety and skin conditions such as acne. Stokes and Pillsbury hypothesized that emotional states might alter the normal intestinal microflora, increase intestinal permeability and contribute to systemic inflammation. Among the remedies advocated by Stokes and Pillsbury were Lactobacillus acidophilus cultures. Many aspects of this gut-brain-skin unifying theory have recently been validated. The ability of the gut microbiota and oral probiotics to influence systemic inflammation, oxidative stress, glycemic control, tissue lipid content and even mood itself, may have important implications in acne. The intestinal microflora may also provide a twist to the developing diet and acne research. Here we provide a historical perspective to the contemporary investigations and clinical implications of the gut-brain-skin connection in acne.

 

http://www.ncbi.nlm....63/?tool=pubmed

Also includes some interesting info on topical probiotics including stuff dating back to 1912. And specifically, topical application boosts ceramide production, the thing we are lacking because of our deficiency in linoleic acid, an important component

'Streptococcus thermophilus, a species found in most yogurts, can increase ceramide production when applied to the skin for 7 days as a cream [58]. This work, which has since been replicated [59,60], is of relevance to acne, particularly when considering that some of the ceramide sphingolipids, most notably phytosphingosine (PS), provide both antimicrobial activity againstPropionibacterium acnes (P. acnes) and direct anti-inflammatory activity [61]. Sphingolipids have been noted to be low in acne [62], and the seasonal loss of ceramides may be a driving force behind much higher dermatological office visits for acne during winter months [63]. Indeed, topical application of 0.2% PS reduced papules and pustules by 89% in a recent 2-month pilot study [61].

And this little tidbit on the IGF1 in dairy being reduced in fermented dairy:

We also find it noteworthy that of three large population studies linking dairy consumption (most notably milk) and acne, none made a positive correlation between fermented dairy (e.g. yogurt) and acne [103-105]. It has been postulated that milk is associated with acne because it contains growth hormones (both synthetically added and naturally occurring) [106]. Acne is certainly driven by insulin-like growth factor I (IGF-I) [107], and IGF-I can be absorbed across colonic tissue [108]. Therefore, it is interesting to note that probiotic bacteria (Lactobacilli in particular) utilize IGF-I during the fermentation process when added to milk, with a resultant 4-fold lower level of IGF-I in fermented vs. skim milk [109].

Good to know!

Wow, thank you for that Alternativista

So I decided to google desquammation enzymes.

Site elaborating on the desquammation process:

Stratum Corneum Anatomy - The Key to Healthy, Attractive Skin which states that the process is:

 

very complex and only parts of this process are fully understood. We do know that several enzymes degrade the

corneodesmosomes

 

in a specific pattern, but we don't know the exact nature of these enzymes or how they become activated to start the exfoliation process. We do know that water and pH play a significant role in the activity of these enzymes.

 

Another way not stripping away your acid mantle with harsh cleansers may help acne.

And a paper: http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CHAQFjAA&url=http%3A%2F%2Fwww.medicaljournals.se%2Facta%2Fcontent%2Fdownload.php%3Fdoi%3D10.1080%2F000155500750012513&ei=q-LgT_LeEKaA2wXOpoTlCw&usg=AFQjCNEsPOUo3dzQqTTnfyhfDPc6Kx0BEA&sig2=JmQfB1CvXhp54BRf6odEYw

The best characterised enzyme so far with a proposed

function in desquamation is stratum corneum chymotryptic

enzyme (SCCE) [6 9].

The mechanisms by which desquamation is regulated remain

to be elucidated. Given the fact that proteolytic degradation

of desmosomes may be a central event in desquamation, a

number of possible regulatory mechanisms can be postulated.

To these belong activation of enzyme precursors, protease

inhibitors in the stratum corneum [14], changes in the lipid

composition of the stratum corneum intercellular space [15],

water content [16, 17] and pH of the stratum corneum [18],

and the action of modifying enzymes such as various

glycosidases [19].

So I decided to google desquammation enzymes.

 

I have two questions. What is the ideal pH of the skin with regards to washing ones face? (The distilled water I use is slightly acidic)

And about desquammation... From my understanding this is caused by the the breakdown of the intercellular junctions called desmosomes that causes the keratinized squamous cells of the stratum corneum to flake off. What I'm not clear on is how this effects overall skin quality.

 

So I decided to google desquammation enzymes.

 

 

I have two questions. What is the ideal pH of the skin with regards to washing ones face? (The distilled water I use is slightly acidic)

 

And about desquammation... From my understanding this is caused by the the breakdown of the intercellular junctions called desmosomes that causes the keratinized squamous cells of the stratum corneum to flake off. What I'm not clear on is how this effects overall skin quality.

 

Your skin should be at about 5.5.Desquammation clears away old dead skin cells revealing a layer of new skin cells. When it happens normally, it leaves fresh, beautiful smooth skin. When it happens unevenly such as in aged or damaged skin, it leaves rough skin. When the cells don't separate and shed freely, they clog pores.

Another way not stripping away your acid mantle with harsh cleansers may help acne.

 

 

 

Amen to that

Your skin should be at about 5.5.Desquammation clears away old dead skin cells revealing a layer of new skin cells. When it happens normally, it leaves fresh, beautiful smooth skin. When it happens unevenly such as in aged or damaged skin, it leaves rough skin. When the cells don't separate and shed freely, they clog pores.

 

Good information thank you

Pathogenesis of Acne vulgaris: what's new, what's interesting and what may be clinically relevant

http://findarticles....ag=content;col1

research of cellular, vascular and proliferative markers via immunohistochemical studies displayed inflammatory events preceding hyperkeratinization. (8) In fact, an increase in CD4 T cells and macrophages was found in clinically un-involved pilosebaceous follicles of acne prone skin. (8) Elevated levels of proinflammatory cytokine interleukin-1 (IL-1) was evident perifollicularly. (8) Furthermore, aberrant integrin expression in uninvolved skin and around inflamed lesions lends additional support that inflammatory events may precede hyperproliferation. (8)

the complete genome of P. acnes strain KPA171202 has been elucidated. (14) The mapping of the genome provides evidence for the existence of a gylcocalyx biofilm which is secreted by P. acnesto act as an "adhesive glue" for the corneocytes in the infundibulum resulting in comedonal acne. (15) Understanding the gylcocalyx polymer layer has clinical relevance in acne therapy. Biofilms act as a protective barrier against antimicrobial agents and may explain why antibiotics are prescribed for months to take effect. (14) Therapy aimed at biofilm formation by P. acnes may be a target source for future acne treatments. Secondly, P. acnes lipase is known to elicit inflammation in acne; however, additional degradative enzymes contributing to follicle wall damage have also been identified following gene sequencing. These include endoglycoceramidases, sialidase/neuraminidases, proteinases and 5 CAMP factors which all contribute to tissue degradation. (14), (16-17)

Although the exact mechanism of action is unknown, research supports the finding of P. acnes inducing matrix metalloprotein-ases (MMP) in sebum via toll-like receptor 2 (TLR2).18 MMP-1, MMP-9 and MMP-13 were identified in acne sebum and thought to originate from keratinocytes and sebocytes. (18) In addition, levels of MMP diminished with clinical improvement of acne lesions following therapy. (18), (19) In fact, treatment of primary human monocytes with all-trans retinoic acid (ATRA) significantly decreased MMP-9 expression. (19) These results indicate that MMP may contribute as one of the mediators in the inflammatory phase of acne vulgaris.

I just noticed something here. The same mutated enzyme we acne prone people may have that inhibits retinoid production in our skin may also inhibit vitamin D production. See the earlier post on beta carotene and retinoid production See also my Diet for Clear skin blog post of a recipe for sweet potato and greens soup. Try it! http://dietforclearskin.blogspot.com/2013/02/hot-spicy-bowl-of-vitamin-for-your-skin.html

So perhaps we need to supplement, even if we try to get it from the sun. Although you should try to get it from the sun as well as some researchers believe we need vitamin D sulfate for some of the functions vitamin D performs. And this has to be made in your body from cholesterol sulfate. Also, that same bit of sun exposure might trigger the conversion of beta carotene to retinoids.

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

Also, because oxidized lipids in the skin are considered a culprit in acne formation and benzoyl peroxide is an oxidizer, I decided to look up some studies:

This one is about topical spearment reducing the harm from BP in mice:

http://www.ncbi.nlm.nih.gov/pubmed/11039327 "The result suggests that spearmint is an effective chemopreventive agent that may suppress BPO-induced cutaneous oxidative stress, toxicity and hyperproliferative effects in the skin of mice."

And this one is about retinoic acids reducing the harm from BP

http://www.ncbi.nlm.nih.gov/pubmed/15225900

Also, because oxidized lipids in the skin are considered a culprit in acne formation and benzoyl peroxide is an oxidizer, I decided to look up some studies:

This one is about topical spearment reducing the harm from BP in mice:

http://www.ncbi.nlm.nih.gov/pubmed/11039327 "The result suggests that spearmint is an effective chemopreventive agent that may suppress BPO-induced cutaneous oxidative stress, toxicity and hyperproliferative effects in the skin of mice."

And this one is about retinoic acids reducing the harm from BP

http://www.ncbi.nlm.nih.gov/pubmed/15225900

 

 

 

 

Also, because oxidized lipids in the skin are considered a culprit in acne formation and benzoyl peroxide is an oxidizer, I decided to look up some studies:

This one is about topical spearmint reducing the harm from BP in mice:

http://www.ncbi.nlm.nih.gov/pubmed/11039327 "The result suggests that spearmint is an effective chemopreventive agent that may suppress BPO-induced cutaneous oxidative stress, toxicity and hyperproliferative effects in the skin of mice."

And this one is about retinoic acids reducing the harm from BP

http://www.ncbi.nlm.nih.gov/pubmed/15225900

I think it's a little simplistic to shun away from BP just because its oxidizing effect. Yes, inflammation is very bad for the skin and probably the very thing that triggers the acne formation process.

At the same time BP can reduce inflammation in the skin. It destroys the bacteria that escalate inflammation and also the cells that initiate the inflammatory process in the skin.

Not to mention the fact that BP reduces acne and redness of the skin. Though, when used improperly, it can also damage the skin.

Also, if you want to reduce inflammation, why bother with spearmint oil or other herbal stuff? Straight vitamins B3, C and E are likely to be much more effective - not to mention easier to find in products.

Many things are anti inflammatory. So why apply something that causes harm?

BP never reduced my acne. And it increases redness and irritation. The forum is filled with people that say the same.

I dont know why the researchers chose to use spearmint oil on the mice.

 

 

 

 

Also, because oxidized lipids in the skin are considered a culprit in acne formation and benzoyl peroxide is an oxidizer, I decided to look up some studies:

This one is about topical spearment reducing the harm from BP in mice:

http://www.ncbi.nlm.nih.gov/pubmed/11039327 "The result suggests that spearmint is an effective chemopreventive agent that may suppress BPO-induced cutaneous oxidative stress, toxicity and hyperproliferative effects in the skin of mice."

And this one is about retinoic acids reducing the harm from BP

http://www.ncbi.nlm.nih.gov/pubmed/15225900

I think it's a little simplistic to shun away from BP just because its oxidizing effect. Yes, inflammation is very bad for the skin and probably the very thing that triggers the acne formation process.

At the same time BP can reduce inflammation in the skin. It destroys the bacteria that escalate inflammation and also the cells that initiate the inflammatory process in the skin.

Not to mention the fact that BP reduces acne and redness of the skin. Though, when used improperly, it can also damage the skin.

Also, if you want to reduce inflammation, why bother with spearmint oil or other herbal stuff? Straight vitamins B3, C and E are likely to be much more effective - not to mention easier to find in products.

Many things are anti inflammatory. So why apply something that causes harm?

BP never reduced my acne. And it increases redness and irritation. The forum is filled with people that say the same.

Yes, this. Anything that causes an oxidative effect similar to a sunburn is not ok in my book. Not to mention tumor inducing in mice. If BP, alone, has genuinely reduced a person's redness, that person has iron skin, and is a rarity amongst human beings.

Many things are anti inflammatory. So why apply something that causes harm?

 

BP never reduced my acne. And it increases redness and irritation. The forum is filled with people that say the same.

There's little evidence that BP, when used properly, causes any harm. And just like every other medicine out there, BP has both positive and negative effects. The art of medicine comes in choosing medicines that do more good than harm.

If BP reduced your acne, then you are among the minority. The other sections of this forum are filled with people who say that BP indeed has reduced their acne and skin redness. Not to mention tens and tens of clinical studies that show efficacy from BP.

Why use BP? Because at the moment it's one of the best anti-acne topicals. No 'natural ingredient' has similar demonstrated efficacy. Some antioxidants, like niacin and vitamin C derivates, show promise and might even turn out to be more effective than BP. That's for the future science to show. But it doesn't take away the fact that BP does work.

 

 

Many things are anti inflammatory. So why apply something that causes harm?

 

BP never reduced my acne. And it increases redness and irritation. The forum is filled with people that say the same.

There's little evidence that BP, when used properly, causes any harm. And just like every other medicine out there, BP has both positive and negative effects. The art of medicine comes in choosing medicines that do more good than harm.

If BP reduced your acne, then you are among the minority. The other sections of this forum are filled with people who say that BP indeed has reduced their acne and skin redness. Not to mention tens and tens of clinical studies that show efficacy from BP.

Why use BP? Because at the moment it's one of the best anti-acne topicals. No 'natural ingredient' has similar demonstrated efficacy. Some antioxidants, like niacin and vitamin C derivates, show promise and might even turn out to be more effective than BP. That's for the future science to show. But it doesn't take away the fact that BP does work.

And this forum is filled with people for whom it didn't work. And with people who chose not to use medicines that cause harm.

And this forum is filled with people for whom it didn't work. And with people who chose not to use medicines that cause harm.

This forum is also filled with people who haven't made much progress with their acne in years. So not much of an argument.

 

And this forum is filled with people for whom it didn't work. And with people who chose not to use medicines that cause harm.

This forum is also filled with people who haven't made much progress with their acne in years. So not much of an argument.

I believe the argument here is still that benzoyl peroxide works for some, and doesn't for others. And for the people it does work for, they are still subjecting their skin to extremely high levels of oxidative stress, which causes the redness, dryness, itchiness, and long term skin damage from free radicals. So...while it may be effective at treating acne for many people, it comes with a price.

The same can be said for most if not all modern medicines. They may serve the purpose they are prescribed for, but they come with a whole host of side-effects that interfere with other important metabolic processes. They are band-aid fixes, and most illness/disease can be prevented and even reversed via proper nutrition and avoidance of toxic foods so commonly found in the western diet.

Also, what about green tea cream? Apparently there was a study conducted by a Dr. Jennifer Gan-Wong from the Memorial Medical Center in the Philippines that showed a 3% concentration of green tea cream was as effective at treating acne as a 4% concentration of benzoyl peroxide. I wish i could find the actual study itself. It is cited repeatedly, but i'd still love to see the study. I think you have to pay a monthly fee to get access to some of these studies, which is unfortunate.

I believe the argument here is still that benzoyl peroxide works for some, and doesn't for others. And for the people it does work for, they are still subjecting their skin to extremely high levels of oxidative stress, which causes the redness, dryness, itchiness, and long term skin damage from free radicals. So...while it may be effective at treating acne for many people, it comes with a price.

The same can be said for most if not all modern medicines. They may serve the purpose they are prescribed for, but they come with a whole host of side-effects that interfere with other important metabolic processes. They are band-aid fixes, and most illness/disease can be prevented and even reversed via proper nutrition and avoidance of toxic foods so commonly found in the western diet.

Also, what about green tea cream? Apparently there was a study conducted by a Dr. Jennifer Gan-Wong from the Memorial Medical Center in the Philippines that showed a 3% concentration of green tea cream was as effective at treating acne as a 4% concentration of benzoyl peroxide. I wish i could find the actual study itself. It is cited repeatedly, but i'd still love to see the study. I think you have to pay a monthly fee to get access to some of these studies, which is unfortunate.

 

 

 

And this forum is filled with people for whom it didn't work. And with people who chose not to use medicines that cause harm.

This forum is also filled with people who haven't made much progress with their acne in years. So not much of an argument.

It has a few people that haven't made much progress, including some who have real health issues. Most people who clear their skin stop posting regularly. But the forum is filled with how I cleared my skin threads.

The value of green tea/EGCG has been known for a while, but this study identifies several factors affected by topical EGCG

Epigallocatechin-3-Gallate Improves Acne in Humans by Modulating Intracellular Molecular Targets and Inhibiting P. acnes.
[url= http://www.ncbi.nlm.nih.gov/pubmed?term=Yoon JY[Author]&cauthor=true&cauthor_uid=23096708]Yoon JY

Source
Acne Research Laboratory, Seoul National University Hospital, Seoul, South Korea.

Abstract

Acne vulgaris is a highly prevalent skin disorder characterized by hyperseborrhea, inflammation, and Propionibacterium acnes overgrowth. Only isotretinoin and hormonal therapy reduce sebum production. To identify a new drug candidate that modulates sebum, we examined the effects of EGCG, the major polyphenol in green tea, on human SEB-1 sebocytes and in patients with acne. In SEB-1 sebocytes, we found that EGCG reduced sebum by modulating the AMPK-SREBP-1 signaling pathway. EGCG also reduces inflammation by suppressing the NF-B and AP-1 pathways. EGCG also induces cytotoxicity of SEB-1 sebocytes via apoptosis and decreases the viability of P. acnes, thus targeting almost all the pathogenic features of acne. Finally, and most importantly, EGCG significantly improved acne in an 8-week randomized, split-face, clinical trial, and was well tolerated. Our data provide a therapeutic rationale for the use of EGCG in acne.

The value of green tea/EGCG has been known for a while, but this study identifies several factors affected by topical EGCG

There are also a few other green tea studies. The problem is that none of them are definitive. The study you referred was mostly in vitro, though it also had an in vivo part. These studies are interesting and provide some evidence for green tea and EGCG but the problem is that they don't have proper controls. Once we see a few studies with 100 or so participants that compare EGCG cream to BP head to head then I can say that there's reasonably good evidence for it. Such studies exists for vitamin B3 and vitamin C derivates.

I would also add topical vitamin b5 to the list. It was greatly reduced the oiliness in my face if not acne. If there is a moisturizer with high amounts of B5, B3, C, E, zinc, EGCC, Thyme and hyalauronic acid then there should not be any chance of acne at all.

This article about a study involving the mapping of the genomes and identifying several different strains od P. Acnes finds a strain predominant in clear skin. Theorizes that it provides protection against harmful microbes in the skin similar to the way beneficial flora do in your intestines.

http://news.sciencemag.org/sciencenow/2013/02/got-pimples-you-may-need-better-.html?ref=hp

In addition to the many ways diet and lifestyle affects your acne by affecting the function of the various organs involved in managing hormones and inflammation: liver, gut, adrenals, thyroid, brain, etc. There are some pathways and systems involved. Both of the below are studies looking into how isotretinoin tends to clear acne. Because they've been prescribing it to children for a couple of decades without really know what it does.

mTORC1 signaling:
Dietary intervention in acne: Attenuation of increased mTORC1 signaling promoted by Western diet
http://www.landesbioscience.com/journals/dermatoendocrinology/article/19828/?show_full_text=true full text avialable.
The western diet habits that promote the mTORC1 signaling include high glycemic meal habits and dairy.

The purpose of this paper is to highlight the endocrine signaling of Western diet, a fundamental environmental factor involved in the pathogenesis of epidemic acne. Western nutrition is characterized by high calorie uptake, high glycemic load, high fat and meat intake, as well as increased consumption of insulin- and IGF-1-level elevating dairy proteins. Metabolic signals of Western diet are sensed by the nutrient-sensitive kinase, mammalian target of rapamycin complex 1 (mTORC1), which integrates signals of cellular energy, growth factors (insulin, IGF-1) and protein-derived signals, predominantly leucine, provided in high amounts by milk proteins and meat.......

It is conceivable that isotretinoin may downregulate mTORC1 in sebocytes by upregulation of nuclear levels of FoxO1.

Fox01 deficiency

The role of transcription factor FoxO1 in the pathogenesis of acne vulgaris and the mode of isotretinoin action. http://www.ncbi.nlm.nih.gov/pubmed/20930691

Nuclear FoxO1 deficiency is the result of increased growth factor signaling with activated phosphoinositol-3-kinase (PI3K) and Akt kinase during growth hormone signaling of puberty and increased insulin/IGF-1 signaling due to consumption of insulinotropic milk/dairy products as well as hyperglycemic carbohydrates of Western diet.

J Dtsch Dermatol Ges. 2010 Feb;8(2):105-14. doi: 10.1111/j.1610-0387.2010.07344.x.
FoxO1 - the key for the pathogenesis and therapy of acne?
[Article in English, German]
Melnik BC.
Source
Department of Dermatology, Enviromental Medicine and Health Theory, University of Osnabruck, Germany. [email protected]
Abstract
Five main factors play a pivotal role in the pathogenesis of acne: androgen dependence, follicular retention hyperkeratosis, increased sebaceous lipogenesis, increased colonization with P. acnes, and inflammatory events. This paper offers a solution for the pathogenesis of acne and explains all major pathogenic factors at the genomic level by a relative deficiency of the nuclear transcription factor FoxO1. Nuclear FoxO1 suppresses androgen receptor, other important nuclear receptors and key genes of cell proliferation, lipid biosynthesis and inflammatory cytokines. Elevated growth factors during puberty and persistent growth factor signals due to Western life style stimulate the export of FoxO1 out of the nucleus into the cytoplasm via activation of the phos-phoinositide-3-kinase (PI3K)/Akt pathway. By this mechanism, genes and nuclear receptors involved in acne are derepressed leading to increased androgen receptor-mediated signal transduction, increased cell proliferation of androgen-dependent cells, induction of sebaceous lipogenesis and upregulation of Toll-like-receptor-2-dependent inflammatory cytokines. All known acne-inducing factors exert their action by reduction of nuclear FoxO1 levels. In contrast, retinoids, antibiotics and dietary intervention will increase the nuclear content of FoxO1, thereby normalizing increased transcription of genes involved in acne. Various receptor-mediated growth factor signals are integrated at the level of PI3K/Akt activation which finally results in nuclear FoxO1 deficiency.

Let's look at this, as I've never really explored the role of Fox01 before.

J Dtsch Dermatol Ges. 2010 Feb;8(2):105-14. doi: 10.1111/j.1610-0387.2010.07344.x.
FoxO1 - the key for the pathogenesis and therapy of acne?
[Article in English, German]
Melnik BC.
Source
Department of Dermatology, Enviromental Medicine and Health Theory, University of Osnabruck, Germany. [email protected]
Abstract
Five main factors play a pivotal role in the pathogenesis of acne: androgen dependence, follicular retention hyperkeratosis, increased sebaceous lipogenesis, increased colonization with P. acnes, and inflammatory events. This paper offers a solution for the pathogenesis of acne and explains all major pathogenic factors at the genomic level by a relative deficiency of the nuclear transcription factor FoxO1. Nuclear FoxO1 suppresses androgen receptor, other important nuclear receptors and key genes of cell proliferation, lipid biosynthesis and inflammatory cytokines. Elevated growth factors during puberty and persistent growth factor signals due to Western life style stimulate the export of FoxO1 out of the nucleus into the cytoplasm via activation of the phos-phoinositide-3-kinase (PI3K)/Akt pathway. By this mechanism, genes and nuclear receptors involved in acne are derepressed leading to increased androgen receptor-mediated signal transduction, increased cell proliferation of androgen-dependent cells, induction of sebaceous lipogenesis and upregulation of Toll-like-receptor-2-dependent inflammatory cytokines. All known acne-inducing factors exert their action by reduction of nuclear FoxO1 levels. In contrast, retinoids, antibiotics and dietary intervention will increase the nuclear content of FoxO1, thereby normalizing increased transcription of genes involved in acne. Various receptor-mediated growth factor signals are integrated at the level of PI3K/Akt activation which finally results in nuclear FoxO1 deficiency.

So, they name 5 major factors in the pathogenesis of acne:
androgen dependence, follicular retention hyperkeratosis, increased sebaceous lipogenesis, increased colonization with P. acnes, and inflammatory events.

All those factors are related to a relative deficiency of the nuclear transcription factor FoxO1.

Nuclear FoxO1 suppresses androgen receptors, genes involved in cell proliferation and lipid biosynthesis. and inflammatory cytokines.

Elevated growth factors due to puberty OR Western diet and lifestyle decrease Fox01

This leads to increased androgen receptor sensitivity, increased cell proliferation, and increase in inflammatory cytokines. I have to look into what 'induction of sebaceous lipogenesis' means, exactly.

Retinoids, antibiotics work by increasing FoxO1 and so will dietary interventions. I.e. avoiding high glycemic and insulinotropic diet habits.

'thereby normalizing increased transcription of genes involved in acne' - in other words, it flips some genetic switches.

Bioactive Dietary Factors and Plant Extracts in Dermatology

Book excerpt on discussing mTorC1,Fox01, and the phos-phoinositide-3-kinase (PI3K)/Akt pathways

http://books.google.com/books?id=kzKqMAkJw3UC&pg=PA404&lpg=PA404&dq=mTORC1+Signaling+acne&source=bl&ots=-wiKYnAKR-&sig=DlCxnkX51Iuh72uRm-tMDXBLFLY&hl=en&sa=X&ei=e0T5UZbqHYGY9QSbzoFw&ved=0CIMBEOgBMAk#v=onepage&q=mTORC1%20Signaling%20acne&f=false

I wish I could copy and paste.

Further down it mentions the role of a high intake of Branched Chain Amino Acids from dairy and meat (especially leucine, especially in young body builders and athletes) May also increase mTorc1 signaling.

And then, after the skip, it starts talking about resveraterol inhibits mTorc1.