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 . 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    . Other oxidised lipids can also stimulate keratinocyte proliferation and inflammatory responses . Squalene oxidation produces free radicals and ROS, which may initiate the early inflammation seen in acne 
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   . 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 
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** 
- 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 .
* Lipoxygenase and leukotriene B4 can promote inflammation in acne, even without P. acnes . Leukotriene B4 is a chemoattractant capable of recruiting ROS-generating neutrophils, whose inhibition has been shown to improve acne 
** The irradiated squalene caused excessive growth and hyperkeratosis of the epithelium and proliferation of sebaceous glands whereas regular squalene didn’t have these effects 
*** 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 
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 
People with acne tend to have lower antioxidant levels/activity and higher lipid peroxidation in serum than controls (lower serum glutathione and glutathione peroxidase , lower vitamin A and E (see table)  and low SOD activity and higher MDA )
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 
- Selenium and vitamin E supplementation improved acne and glutathione peroxidase levels (which were associated) 
* It’s odd that those in the mild acne category have higher SOD activity and lower MDA levels, a super-compensatory response perhaps?