Squalene Peroxidation in Acne Vulgaris: Linking Sebum Oxidation to Inflammation and Comedogenesis

Acne vulgaris is a skin condition that affects millions of people worldwide and can cause significant emotional distress. The current treatments primarily target bacterial colonization and sebum production and often provide inconsistent results because they do not address the oxidative stress and lipid peroxidation that can worsen acne. One of the emerging areas of interest in understanding acne development is the role of squalene peroxidation. Squalene constitutes about 10-15% of the total sebum lipid content and highly susceptible to oxidation due to the presence of multiple double bonds which makes it a prime candidate for peroxidation where oxidative degradation of squalene can form squalene monohydroperoxides, which are highly comedogenic and can worsen the inflammatory processes associated with acne. The peroxidation of squalene is believed to be triggered by UV radiation, environmental pollutants, and the presence of Cutibacterium acnes bacteria on the skin. To this end, new study published in Pharmaceuticals Journal and conducted by PhD student Giorgia Condrò, Roberta Sciortino, and Professor Paola Perugini from the Department of Drug Sciences at the University of Pavia developed a new in vivo method to extract and quantify squalene from acne-prone skin and correlated their findings with biophysical skin parameters including sebum content, protein levels, and transepidermal water loss (TEWL).

First, the researchers performed an in vitro experiment to quantify the number of peroxides formed in squalene when exposed to oxidative conditions and used sodium thiosulfate titration to measure the peroxide number, which indicates the amount of hydroperoxides present.  They exposed the samples to a solar simulator to mimic the oxidative stress induced by UV radiation and found that squalene exhibited a significant increase in peroxidation which indicates its high susceptibility to oxidative degradation compared to the controls. Afterward, the authors extracted and quantified squalene from acne-prone and healthy skin where they collected sebum samples using D-Squame adhesive discs from the forehead, chin, cheeks, and shoulders of both acneic and healthy volunteers then analyzed the extracted sebum using high-performance liquid chromatography (HPLC) and found a substantially higher concentration of squalene in acne-prone skin. The team also found that highest concentrations of peroxide squalene to be in the forehead (7.3%) and notable amount in the inflamed chin 4.7%, and the non-inflamed chin 2.9%. This differential distribution of peroxide squalene highlights its potential role in localized inflammation and comedogenesis. Moreover, the authors measured several biophysical parameters of the skin, including pH,  TEWL, protein content, and sebum levels and found that acne-prone skin had higher TEWL and protein content indicative of a compromised skin barrier function. Additionally, sebum levels were significantly higher in acneic subjects, and correlated with the increased presence of squalene and its peroxide form. In conclusion, the study conducted by Giorgia Condrò, Roberta Sciortino, and Professor Paola Perugini provided compelling evidence that squalene and its oxidized form, peroxide squalene, are significantly elevated in acne-prone skin compared to healthy skin which shows the pathogenic role of lipid peroxidation in the development of acne, particularly in forming comedones and inflammatory lesions. Moreover, squalene and its peroxide could act as lipid biomarkers for acne-prone skin which can be used as a new tool for better diagnosis and monitoring acne severity and progression, and provide a more targeted approach to acne management. Their findings also suggests that oxidative stress plays an important role in acne development, therefore, therapeutic strategies that target and reduce oxidative stress could be highly effective including the use of antioxidants and drugs that inhibit lipid peroxidation, potentially offering a new acne treatment. Additionally, sunscreens and skincare products that have antioxidant ingredients can be recommended to protect the skin from oxidative stress and reduce the risk of acne flare-ups.