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What follows is a guest post by an experienced, thorough and brilliant acne advocate who runs the site and blogs at   I followed Seppo’s advice to use a topical antioxidant, and that has been the nail in my acne’s coffin.  It has also been the best thing I have done for the overall softness, radiance, and evenness in tone of my skin in ages.  Seppo’s blog is incredible for acne — the real deal.  All of which is to say, this is good stuff.  For acne and hormones, I trust me.  For acne and the gut, I trust Chris Kresser.  For topical approaches , antioxidants, and explaining how they all tie together, I present Seppo Puusa.


Acne: Thinking Beyond Hormones

Acne is a common co-occurrence of PCOS and other hormonal imbalances. This causes some people to come to the unfortunate conclusion that they have to ‘fix their hormones’ before they can get over acne. While it’s true that hormones are a big part of acne it’s equally true that there’s more to acne than hormones. And the ways to deal with acne need not be limited to hormonal fixes.

In this post I want to introduce you to the other side of acne and hopefully share some ways to get clear that go beyond hormones.

Let’s understand acne first

Let’s start by taking a moment to understand why you get acne. After reading hundreds of studies, I’ve realized there’s a rather simple explanation to acne, and we can explain most acne cases with this model.


 Over the past decade scientific understanding of acne has moved away from bacteria causing acne towards inflammatory origin of the disease. More specifically, good evidence exists to show inflammatory damage to sebum (sebum oxidation) is what really triggers the acne formation process. Other ‘causes’ of acne (diet, gut issues, hormones, etc.) simply set the conditions for sebum oxidation to happen.

Sebum oxidation as the primary cause of acne

Sebum is composed of many fatty acids; one that we are interested is called squalene. Squalene is problematic because it suffers massive oxidative damage when exposed to UV rays (and probably also to other inflammatory insults) and turns into squalene peroxide. Squalene peroxide is massively comedogenic. A 2010 review had this to say:

Comedogenicity of squalene peroxides has been demonstrated in animal experiments in which comedones have been induced by exposing rabbit ears to irradiated squalene. The degree of squalene peroxidation was found to correlate positively with the size of the comedones elicited. In addition, the treatment of ear skin with squalene peroxidation by-products caused marked hyperplasia and hyperkeratosis of the epithelium in follicular infundibulum, and increased the proliferation of the sebaceous glands.

(Lipid Mediators in Acne. Monica Ottaviani, Emanuela Camera, Mauro Picardo. Mediators Inflamm. 2010; 2010: 858176.

Let me translate that from science-speak to clear English. Applying squalene peroxide to rabbit ears caused comedoes (pimples) to form, and the severity of acne was related to the degree of damage squalene suffered. Squalene peroxide also caused abnormally high rate of skin cell growth and sebum and keratin production; keratin is a tough protein that binds skin cells together, excess keratin production is a feature in many skin conditions.

These are ideal conditions for microcomedoes to form. Microcomedoes are the earliest stages of a pimple, and form before bacteria colonizes the skin pore. This is why many researchers now believe inflammation is the trigger that sets off the acne formation process.

Noninflamed lesions, which are first visible during the adrenarche in acne-prone individuals, do not contain propionibacteria. Comedogenesis appears to be independent of bacterial infection and may be driven by high levels of bioactive interleukin-1α derived from ductal hyperkeratinocytes.

(Is Acne an Infection of Blocked Pilosebaceous Follicles? Anne Eady, Jonathan H. Cove. American Journal of Clinical Dermatology. July 2000, Volume 1, Issue 4, pp 201-209.

In other words, the very earliest stages of a pimple don’t contain bacteria. Start of the acne formation process seems to be triggered by inflammatory signals from keratin-producing cells (the result of exposure to squalene peroxide) and has nothing to do with bacteria.

There’s even evidence to show that bacterial colonization of a blocked pore is the result of inflammatory damage and might have not even be possible without it.

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.

(Clinical implications of lipid peroxidation in acne vulgaris: old wine in new bottles. Whitney P Bowe, Alan C Logan. Lipids in Health and Disease 2010, 9:141.

This is not to say that bacteria wouldn’t affect acne, they just enter the picture later. Once a microcomedo has formed, bacteria colonize it and massively increase inflammation in the area. This is what turns blocked pores into painful cysts. But none of that would happen without the initial inflammatory damage to sebum.

To put simply, there’s no acne without oxidative damage to sebum. And that’s why most of your efforts to get over acne should be aimed at preventing that from happening. A case can also be made for antibacterial agents to control the pimples that form despite your efforts to prevent them – it will happen because of genetics; you can now go and thank your parents.

Setting the conditions for sebum oxidation to happen

Obviously there’s more to acne than this. But I wanted to stress the importance of sebum oxidation as it seems to be the point of convergence in acne, and all the other factors merely set the conditions for sebum oxidation to take place.

Beyond the skin, there are two ‘things’ that cause acne: hormones and inflammation. Here’s a good analogy to understand how these affect acne. I’m a guy, so hopefully you’ll forgive me the engineering reference.

This masterpiece of art represents a hose with 2 inlets. The hose is a skin follicle (or skin pore) and the inlets represent hormones and inflammation.

The more imbalanced your hormones are and the more systemic inflammation you are under, the more pressure the hose has to bear. At some point the pressure gets too high and the hose ruptures. So it’s not that hormones or inflammation (via diet, gut, stress, etc.) cause acne as such, but they put pressure the skin, and if that pressure gets too high, then you get acne.

Obviously we aren’t talking about physical pressure here. Rather, it takes on a different form:

  • Hormones affect both sebum production and composition. Acne patients not only produce a lot more sebum but sebum also has proportionally more squalene. Diet-acne studies have shown that reducing the glycemic index of diet reduces the hormones associated with acne and this reduces sebum production and alters sebum composition.
  • Systemic inflammation affects the skin by depleting antioxidant reserves. Antioxidants of course protect you from inflammatory damage. The primary antioxidant in the skin is vitamin E, and studies have shown a tight correlation between secretion of squalene and vitamin E; suggesting vitamin E is used to protect squalene from oxidizing and the harmful consequences it has. There’s evidence that the antioxidant system just cannot cope with the demand in acne. For example, earlier this month a study came out that showed acne patients have significantly lower blood levels of vitamins A and E and zinc. Other studies have looked at antioxidant and inflammatory markers in blood and skin and have found similar results. Shortage of antioxidants leaves sebum vulnerable to inflammatory damage and opens the door for acne.

So in summary, hormones regulate how much sebum the skin produces and the fatty acid composition of sebum. If your skin produces more sebum it also needs more antioxidants protection. Inflammation depletes finite antioxidant reserves and may leave sebum vulnerable to inflammatory damage.  Without adequate antioxidant protection squalene suffers oxidative damage and forms squalene peroxides. Squalene peroxide is massively comedogenic, causes hyperkeratosis, and sets the stage for acne.

Beyond the obvious solutions

Stefani has already talked a lot about the reasons behind hormonal abnormalities and inflammation in acne. These include diet, PCOS, stress and gut issues. There’s also no shortage of good dietary advice. In fact, the basic paleo diet works quite nicely for acne.  See Stefani’s stuff on hormonal acne here.   See Chris Kresser’s here.  And Liz Wolfe’s unparalled and excellent acne guide here. (Stefani promises to write a review of it a.s.a.p.)

But I really hope that the framework we just talked about helps you to think about acne more broadly. Diet and other hormonal fixes should help your skin, but they need not be your only options.

Here are some other options you can consider:

  • Are you too harsh on your skin? Skincare products can both help and harm your skin. Benzoyl peroxide for example can be very effective, but at the same time it’s been shown that a single application of BO depletes 50% of vitamin E from your skin. It’s easy to see how relying on BP too much can harm your skin. Don’t take this to mean you should never use BP or other ‘chemicals’ on your skin. They can help when used properly. [See this post for more]
  • Use protection. The skin is constantly exposed to inflammatory damage (think UV, air pollution, chlorine in swimming pools) that can harm the skin barrier function and leave the skin vulnerable. Applying some moisturizer in the morning goes a long way in keeping your skin healthy. Also remember to apply some after you’ve been swimming.
  • Use topical antioxidants. And while you are shopping for moisturizer make sure to pick something that has antioxidants. Several studies have now shown that topical antioxidants are at least as effective as topical antibiotics or benzoyl peroxide in treating acne. Vitamin B3 and a vitamin C precursor sodium ascorbyl phosphate have the best supporting evidence. Other promising ingredients include EGCG (found in green tea), seaweed extracts and resveratrol. [I wrote about topical antioxidant studies here]
  • Consider taking an antioxidant supplement. Studies have also shown supplemental antioxidant could be helpful in acne, though the data is much weaker. Supplements that have been shown to be effective include zinc and N-Acetyl Cysteine (NAC), a precursor to antioxidant enzyme glutathione.

  • (This is a Stefani interjection:  Seppo says from his blog on with respect to this graph: “As you can see, the reduction in pimple count is practically linear for both N-Acetylcystein and silymarin supplements. After 8 weeks both supplements reduced acne lesions by about 50%. Selenium supplementation also showed a nice reduction, if not quite as quick as with the other 2 supplements. In contrast, there was no real change in the placebo group. I should note that this study was single-blinded, so the participants didn’t know which supplement they received.”

People often have an unfortunate tendency to latch on a single factor as The Cause of acne (I just need to fix my diet and then I will get clear, or this darn PCOS is making a mess of my skin). While there is truth to these sentiments it’s good to remind yourself of the big picture.

Acne is the result of a combination of genetics, hormones and inflammation. Together they conspire to create the perfect conditions for sebum oxidation to take place, which then kick starts the acne formation process. Improving your diet and taking steps to address hormonal imbalances will help, but they need not to be your only treatment options.

While it’s true that hormones are a big part of acne it’s equally true that there’s more to acne than hormones. And the ways to deal with acne need not be limited to hormonal fixes.



Author blurb

Seppo Puusa is the author of the blog – The place for rational, science-based advice on natural and alternative acne treatments.

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