Epigenetics, Diet & Acne

Avoiding habits that elevate growth factors (or growing out of puberty) changes expression of genes involved in acne.

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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 Osnabrück, Germany. melnik@t-online.de

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 changes genetic expression or 'flips some genetic switches'.

Your skin isn't dead leather & your sebum isn't dead grease. They are ecosystems for enzymes and other substances that play vital roles in skin function. Your sebum contains living cells that produce these substances. Substances that protect and exfoliate. That inhibit DHT production which is a major factor in oily skin, acne and male pattern baldness. Substances that inhibit melanin, reducing hyperpigmentation, Substances that produce retinoids & ceramides.

All those things you pay big money for in moisturizers & creams are made by your skin!  Or would be if you would stop impairing its ability to function. Those ceramides & other lipids are also stripped away by cleansers. Emulsifying agents are even in lotions & creams you think are helping your skin. They are what keep the watery & oily ingredients mixed together so you don't have to shake the bottle before using, because that would be too much to ask. 

Stripping your skin of all these things makes it hard for skin to function and causes the problems we then try to solve with more products. Soaps, cleansers and topicals prevent your skin from functioning.

Intro/definitions

 Acid Mantle - a layer of sebum and sweat that, among other things, makes the surface of your skin slightly acidic which inhibits the overgrowth of harmful microbes. In addition, the various enzymes involved in normal cell desquammation (exfoliation) need an acidic environment to function. Even store bought BHA and AHA topicals need to be the correct PH to function.

Soaps are alkaline and strip it away. It can take hours to recover during which time your skin is vulnerable to microbes and cells don't exfoliate freely without clogging pores. Tap water in most areas is also slightly alkaline, but your skin should recover from the tap water fairly quickly.

Sebum/lipid permeability barrier

- Normal sebum contains enzymes that inhibit the formation of DHT, the form of testosterone that aggravates acne. It also contains enzymes that dissolve the desmosomes that bind your skin cells together so they can exfoliate normally.

Linoleic acid is a major component of normal sebum. A deficiency in linoleic acid has been found to be involved in many skin issues including acne, excema, atopic dermatis, just plain sensitive easily irritated skin, etc. This applies to all mammals. Where linoleic acid is deficient, oleic acid is used. This produces sebum that is greasy looking and sticky which causes skin cells to be clump together and clog pores.

Sphingolipids, ceramides TBC

see http://www.acne.org/messageboard/topic/330732-help-your-skin-function-stop-impairing-it/?do=findComment&comment=3397556

P. Acnes TBC

Washing away your sebum stimulates more production of sebum.

Or at least, the abstract of this peer reviewed paper says so. the full text is available here: http://www.nature.co...df/5610517a.pdf 

" The epidermis is a very active site of lipid synthesis and when the permeability barrier is disrupted by topical solvents or detergents a marked stimulation of sterol, fatty acid, and sphingolipid synthesis occurs. "

-Acne prone skin (as well as other problem prone skin) is deficient in linoleic acid. And this makes the differenct between sebum that protects and makes your skin glow versus sebum that looks greasy and is sticky and clogs pores. As it's unlikely most people don't get enough in their diets (usually too much) there must be something that either impairs getting it into skin/sebum or we metabolize it too fast for it to be used. Or the quality of the high omega 6 PUFA oil is poor and rancid.

Topical application has been shown to be helpful. Grape seed and safflower oils are both over 70% linoleic acid. See this lengthy thread all about the subject in which I try to figure out why our skin/sebum is deficient and find evidence that topical application is helpful: http://www.acne.org/...pical-solution/ Another thread with studies such as one where low levels of linoleic acid coincide with acne vulgaris: http://www.acne.org/...ost__p__3168178

-Blood Sugar Stabilizing Diet habits - Excess insulin stimulates the hormones that cause oily skin. And a low GI diet improves the fatty acid composition of sebum according to a recent study.
-Consuming nutrients that inhibit DHT
-Avoiding dairy which contains a precursor to DHT
-Topical application of things that inhibit DHT - Green Tea, mint tea, licorice extract, linoleic acid, zinc (try mineral makeup & sunscreens) ...


Good fats needed for Sebum Quality:
-Consume more Omega 3 EFA sources (like fish, Omega 3 rich vegetables) and less Omega 6 EFA sources (grains and grain-fed animal products). Also avoid bad fats from fried foods, hydrogenated fats like margarine and crisco.
-Linoleic acid a good Omega 6 that your body uses to make Gamma Linoleic acid and an important component in healthy sebum. Diets high in sugar, alcohol, or trans fats from processed foods, as well as smoking, pollution, stress, aging, viral infections, and other illnesses such as diabetes inhibit the body's ability to make GLA. There are GLA supplements. (but linoleic acid may suppress thyroid hormone function, so don't go overboard)
-Mono-unsaturated fats - Olive oil, avocados...

-Blood sugar stabilizing diet habits- Moderate to low GL meals, no binge eating, etc. Affects body's ability to make GLA (among many other things like hormone balance, inflammation, etc.)

Don't strip away skin oils with harsh cleansers. Chemicals and enzymes in sebum play a role in normal desquamation (exfoliation) of skin cells. It can't do that if you wash it all away. Also, your skin needs to be slightly acidic for these enzymes to function. Most cleansers are alkaline.

Quite a bit of info on nutrients involved in quality sebum and many other factors to do with acne formation in this article:http://www.iinr.org/...eports/ACNE.PDF

Vitamin D

It had previously been shown that defects in the immune system interfere with the skin's ability to produce a peptide called cathelicidin, which is protective against microbial invasion. In many skin diseases, including eczema, a deficiency of cathelicidin correlates with increased infection.

Study participants (14 with atopic dermatitis and 14 without) were all given 4000 IUs of oral Vitamin D3 (cholecalciferol) per day for 21 days. Skin lesions were biopsied before and after the 21-day period. The researchers found that oral vitamin D use by the patients appeared to correct the skin's defect in cathelicidin.

Where I left off copying & pasting content

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Big Food and "The Secrets of Sugar"

You must watch this 45 min doc from Canada's CBC news.  About the evils of sugar & the evils of the big food corporations that produce processed foods.  Much like to tobacco industry in that they both new the dangers, and took steps to discredit scienests, defund research as Americans became sicker and more obese,

While not emphasized in this documentary, sugar affects your skin as well.  It elevates hormones involved in acne formation. It's pro-inflammatory which is involved in acne formation. And it ages your tissues including your skin.

https://www.youtube.com/watch?v=xDaYa0AB8TQ

Better Pancakes

Pancakes!!

Oladyi : Russian Yogurt Pancakes in which the flour is fermented overnight in yogurt.

Grain Free Swedish pancakes. Just cream and eggs.
http://ibelieveinbut...edish-pancakes/
Low-carb, grain-free Swedish pancakes
Ingredients:
1/2 cup heavy cream (ideally raw)
4 eggs
1 tbs butter, melted
pinch of salt
Tools:
1 Swedish pancake pan or regular pan
Spatula
Melt the butter and the cream and add the eggs to it. whisk briskly and add salt.

Coconut flour crepes: http://www.freecocon...ut-flour-crepes
ervings: 4
Preparation Time: 3 minutes

• 1 cup coconut milk*
• 1/4 cup milk
• 3 eggs
• 1/4 cup coconut flour
• 2 tablespoons tapioca flour
• dash of salt
• coconut oil for griddle or pan
  Mix all wet ingredients together then add all dry ingredients. Mix until there are no lumps.
  Spoon onto greased pan or griddle to about 6" in diameter. Batter is runny, so they will be very thin. Coconut flour always takes a while to cook. Flip when the top appears dry and edges are brown. These are quite fragile, so flip carefully. But, they are well worth the effort.
  * For the freshest coconut milk make homemade coconut milk. (See video at this link.)

A commenter said to add another egg and supplied a topping recipe
1 package mixed frozen organic berries
1 tbsp tapioca flour
1 dropper full of liquid stevia
1 teaspoon honey (or more to taste)
1/3 cup water
whipped creme

Heat the berries over low heat. Mix tapioca flour and water until dissolved. When berries are thawed add stevia, honey and water mixture. Stir while bringing to a boil, for about one minute, until mix thickens. Turn off heat.
Add a generous spoon full to top of crepe and a dollop of whipped creme.