Sunday, April 7, 2013

Squalene Oxidation and Oxidative Stress

Squalene Oxidation 

Remember from the last post that people with acne secrete much more squalene (higher proportion in sebum + more sebum).  Squalene has six double bonds, making it susceptible to oxidation and for atmospheric oxygen to bind to it [1].  Squalene oxidation promotes acne and may be necessary to acne to develop. 

Squalene oxidation products promote the formation of comedones.  They stimulate production of keratinocytes, pro-inflammatory cytokines and lipoxygenase*.  They cause histological changes to keratinocytes and suppression immune function, are cytotoxic, irritating to cells and deplete glutathione [1] [2] [3] [4].  Other oxidised lipids can also stimulate keratinocyte proliferation and inflammatory responses [5].  Squalene oxidation produces free radicals and ROS, which may initiate the early inflammation seen in acne [3] 

Squalene oxidation allows P. acnes colonisation of the follicle.  Completely oxidised squalene absorbs a quarter of its molecular weight in oxygen.  Therefore 40ng (not much) of squalene when fully oxidised would be sufficient to deplete the oxygen tension in the follicle, where microgram quantities of pure squalene can be found.  The alteration in oxygen tension from such oxidative stress allows anaerobic bacteria such as P. acnes to colonise the follicle and flourish [1] [3] [4].  P. acnes was once thought to initiate acne, but P. acnes may not be able to colonise the follicle without oxidative stress firstly altering the oxygen tension of the follicle.  So it seems inflammation and oxidative stress initiate acne [4] 

Evidence to support the role of squalene oxidation in acne:

  • Exposing rabbit ears to irradiated squalene can trigger comedones and there was a positive correlation between the degree of squalene peroxidation and size of the comedones** [2]
  • People with acne have a fair bit of squalene oxidation products while controls only had ‘traces’ of them.  One oxidation product called ‘Compound D’ comprised up to 22% of the comedone lipids***, was inversely associated with squalene and seems to be the squalene oxidation product that causes comedones [6]. 

* Lipoxygenase and leukotriene B4 can promote inflammation in acne, even without P. acnes [4].  Leukotriene B4 is a chemoattractant capable of recruiting ROS-generating neutrophils, whose inhibition has been shown to improve acne [3] 

** The irradiated squalene caused excessive growth and hyperkeratosis of the epithelium and proliferation of sebaceous glands whereas regular squalene didn’t have these effects [2] 

*** Remember that squalene comprised a fair bit less than 22% of the sebum lipids in those with acne and there are other squalene oxidation products and unoxidised squalene as well 

**** It’s interesting to note that UV radiation can oxidise squalene, but the prevalence of acne is lower during summer [6] 

Oxidative Stress 

People with acne also show signs of oxidative stress in general, which is consistent with the role of squalene oxidation in acne and suggests a systemic source of oxidative stress for squalene oxidation. 

Skin samples from people with acne show lower glutathione in acne lesions, but also in unaffected areas of the face and on the upper back.  The earliest comedones have lipid peroxidation, and lipid peroxidation increases 4 times as inflamed lesions appear [3] 

People with acne tend to have lower antioxidant levels/activity and higher lipid peroxidation in serum than controls (lower serum glutathione and glutathione peroxidase [3], lower vitamin A and E (see table) [7] and low SOD activity and higher MDA [8])



Consistent with the role of oxidative stress, antioxidants are effective for acne:

  • Topical antioxidants such as zinc and a vitamin C precursor (SAP) are more effective than benzoyl peroxide [3]
  • Selenium and vitamin E supplementation improved acne and glutathione peroxidase levels (which were associated) [9] 

* It’s odd that those in the mild acne category have higher SOD activity and lower MDA levels, a super-compensatory response perhaps?

5 comments:

  1. Olive oil is the main food source of squalene, so I would look for correlations between olive oil and acne. From what I can gather from google, olive oil is more likely to be considered as a treatment.
    Consider this possibility; squalene production is the skin's protective response to oxidative stress. Squalene has similar properties to carotenoids (quenching singlet oxygen radicals).
    Perhaps antioxidants that are effective for acne are replacing squalene, lowering the triggers for its production.
    And irradiated squalene has lost its antioxidant properties, so worsens acne by displacing and oxidizing the protective squalene made by skin.

    In this scenario squalene would be a kind of endogenous default carotenoid; so that increased carotenoids (spirulina would be an easy way to significantly increase catotenoid intake).
    Of course many acne medicines are based on retinol. A quick google search returns stories of spirulina both curing and causing acne.

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    1. Hi George,

      I hope you don't think I'm saying squalene is 'bad'. While I've only looked into it briefly, I would say you're right - squalene seems to have protective properties. Afterall squalene is unique to sebum, so it's probably not there by accident. What's more, if acne were as simple as squalene + singlet oxygen then everyone would have it. So in this case I think we should be looking for a systemic source of oxidative stress/antioxidant depletion

      Retinol does seem very therapeutic for acne via many mechanisms. Just because spirulina can trigger acne in some people doesn't necessarily mean retinol can trigger acne. There are probably compounds in spirulina that can do that in some people.

      And that's the difficultly of acne and some other health problems (often GI ones), they can be so individual. My goal is to look at things that seem to be universal mechanisms.

      Thanks for your comment, you've given me something to look into and think about

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  2. Well I like what your website does to my Google+ profile pic.
    Yes, there can be allergies to spirulina, I chose it for an test case because of its very high mixed carotenoid content relative to its other nutrient constituents. But carotenoids are very unlikely to play any part in allergies.
    Thyroxine causes acne as a side effect and thyroxine and retinol are both factors that control basal metabolic rate. Thyroxine may (given the roles of these 2 factors) increase the movement of retinol into mitochondria, depleting it elsewhere.
    The body can't make carotenoids, retinol, or vitamin E de novo but it can make squalene, which is probably an imperfect substitute - just as meade acids are imperfect substitutes for EFAs when these are deficient...

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  3. Please one of you clarify, are you saying that the body is producing squalene due to a deficiency of this in the body? Would eating olive oil help with acne in that case? I just have a blood test done for nutritional status and was deficient in Oleic Acid (high in olive oil), yet I have terribly oily skin and blackheads/whiteheads, but no pimples. At age 53 this is most bothersome, as I'd have thought my oily skin would be improving at this age, but it's getting worse. Blood work also showed slightly over range prolactin (yes, I'm mildly hypothyroid). I'm female, not yet thru menopause, young looking, fit, but suffer from candida infections, heavy metal toxicity and just found out that I harbor 2 gut infections: H. Pylori & Blastocystic. Health is a challenge these days, one day at a time. Will you please comment further on the olive oil/squalene/oleic connection?

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    1. Hi Libby, George was saying that the body may produce squalene in response to low carotenoids/retinol as an imperfect substitute.

      I don't know whether olive oil will help, seeing as you're low in oleic acid and squalene seems protective, it may do. A quick google search suggests topical olive oil may be therapeutic too. It's probably worthwhile experimenting. On that note, a deficiency in oleic acid sounds odd because the body can make it and it's rather easy to get in the diet.

      I suspect most of your health problems are probably what's behind the acne and are exacerbated by low thyroid function. You should find a good clinician to help you address these areas and discuss stuff like diet and lifestyle, as well the pros and cons of supplements for example selenium, carnosine, zinc and alpha-lipoic acid, which may be helpful.

      I hope you get better soon.

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