Lipid peroxidation & ferroptosis: A greater challenge for oily skin types

Lipid peroxidation is a chemical process involving the oxidative degradation of lipids, particularly polyunsaturated fatty acids (PUFAs) such as arachidonic acid. It´s initiated when free radicals, especially reactive oxidative species, "steal" electrons from lipids, resulting in the formation of lipid radicals and cell damage.

This process occurs through three stages: 

▌Initiation: A free radical (often hydroxyl radical) abstracts a hydrogen atom from a PUFA, creating a lipid radical. 
▌Propagation: The lipid radical reacts with molecular oxygen to form a lipid peroxyl radical, which can then abstract hydrogen  from another lipid, continuing a chain reaction and forming lipid hydroperoxides.
▌Termination: The chain ends when two radicals combine or antioxidants (like vitamin E) neutralise them, forming non-radical products.  [1][2] 

Uncontrolled  lipid peroxidation leads to membrane damage, cell dysfunction and death. While it occurs naturally during aging, external factors such as UV radiation, pollution, and cigarette smoke accelerate lipid peroxidation by generating reactive oxygen species (ROS). These ROS interact with PUFAs in cell membranes, initiating a cascading chain reaction that produces toxic aldehydes like malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE), which contribute to oxidative stress, cellular damage, and programmed cell death mechanisms like apoptosis and ferroptosis [1][2][3]. 

Sebum is primarily composed of saturated fatty acids (e.g., palmitic acid at ~31%) and monounsaturated fatty acids (e.g., sapienic acid at ~21%), but it also contains smaller quantities of PUFAs such as linoleic acid [4][5]. Despite their lower abundance, sebum PUFAs are highly susceptible to peroxidation due to their double-bond structure [1][3].  For example, in acne patients, reduced sebum PUFA levels correlate with inflammatory states, while increased saturated fatty acids exacerbate pro-inflammatory cytokine production [4]. This highlights the dual role of sebum lipids in maintaining skin barrier function and contributing to oxidative damage when peroxidation occurs [4][5].
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Lipid peroxidation plays a role in various skin conditions, including acne and signs of photoaging [6][7], rosacea, psoriasis and eczema.

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OILY SKIN AND LIPID PEROXIDATION

Oily skin is more susceptibility to lipid peroxidation due to increased sebum production and lipid accumulation at the skin surface [8]. The higher concentrations of sebum provides more substrate for oxidation, increasing the risk of barrier damage (membrane disruption), inflammation (triggering cytokine release), breakouts and cell death.

1. Altered sebum composition: UV radiation and pollution induce non-enzymatic oxidation of sebum lipids, generating comedogenic oxidation products that that spark acne-related inflammation [8][9]. The oxidation process particularly affects squalene and unsaturated fatty acids [10].
2. Squalene oxidation: As the most oxidation-prone sebum component, squalene generates pro-inflammatory peroxidation byproducts (e.g., squalene peroxides) when exposed to UV radiation [9][11]. These oxidized derivatives activate aryl hydrocarbon receptor pathways and promote inflammatory responses in keratinocytes [11]. 
3. Barrier integrity disruption: Lipid peroxidation products alter stratum corneum lipid organization, increasing trans-epidermal water loss and permeability. Reduced ceramides (especially Cer[NH] and Cer[AH]) worsen this barrier damage. [9].
4. Sebum viscosity changes: Oxidative modification increases sebum viscosity through formation of lipid peroxides and cross-linked polymers [8]. This thickened sebum causes pore blockage (follicular hyperkeratosis) and comedo formation, creating oxygen-free conditions where acne bacteria thrive [8].

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While lipid peroxidation is a natural byproduct of UV exposure, it is harmful at elevated levels. 
▌UV-mediated oxidation: UVA (320-400 nm) primarily drives non-enzymatic lipid oxidation (free radical pathways and non-radical pathways:oxygen oxidation, ozone reactions), while UVB activates enzymatic pathways (phospholipases, lipoxygenases) for eicosanoid production [9]. Eicosanoids are bioactive signaling molecules derived from polyunsaturated fatty acids (PUFAs) like arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) which regulate inflammation, immunity, and vascular function.
Visible Light (including Blue Light) also contributes to lipid peroxidation.
▌Antioxidant depletion – lowered capacity: Oily skin types often experience an imbalance in antioxidant defenses. Also acne-prone skin has lower vitamin E levels, weakening protection against oxidative damage including squalene peroxidation [8][12]. A hallmark of sebum in acne patients is the presence of lipoperoxides, mainly due to the peroxidation of squalene and a decrease in the level of the major sebum antioxidants [13].
▌Acne inflammation cycle: Excess sebum attracts immune cells (neutrophils) that release damaging reactive chemicals, worsening oxidative stress [8]. This stress triggers lipid peroxidation, where oxidized fats act as inflammatory signals, directly worsening acne. Studies show higher levels of these oxidized fats in acne patients, strongly linked to inflamed lesions [14][15].

FERROPTOSIS AND SKIN HEALTH
Ferroptosis is a type of cell death caused by toxic buildup of damaged fats in cell membranes and is triggered by iron-driven lipid peroxidation when cells can’t neutralize harmful lipid peroxides, mainly due to glutathione peroxidase 4 (GPX4) failure. 

This happens through two key mechanisms:

1. Iron’s role: Iron generates destructive free radicals via Fenton reactions and fuels enzymes like lipoxygenases that oxidize lipids [16][17].
2. GPX4 breakdown: Without enough glutathione (GSH), GPX4 can’t convert toxic lipid peroxides into safe alcohols, causing lethal membrane damage [18][19].

The outcome is that uncontrolled lipid peroxides rupture cell membranes, executing iron-dependent ferroptosis [16].
 
STRATEGIES MANAGING OILY SKIN 

Effective skincare strategies for managing oily and acne-prone skin focuses on at least three key objectives [13]:
▌Inhibit the excessive secretion of sebaceous glands / reduce skin surface lipids
▌Improve the quality of sebum
▌Reduce the occurrence of lipid peroxidation  

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1. Antioxidant-rich skincare: Incorporating topical products containing antioxidants such as vitamins C and E, and Licochalcone A can help neutralize free radicals and prevent oxidative damage to lipids [6]. Licochalcone A has been shown to inhibit lipid peroxidation in keratinocytes (the main cell type in the epidermis) induced by UV radiation [20], and in human dermal fibroblasts exposed to hydrogen peroxide [21].   
2. Melatonin: The hormone melatonin, is widely present in various tissues including the skin and regulates circadian rhythms and promotes sleep. Melatonin can penetrate membranes and mitigate lipid peroxidation and protein oxidation, as well as oxidative damage to the mitochondria and DNA caused by UVR [22]. 
3. Daily cleansing and regular exfoliation: Gentle exfoliants such as salicylic acid (a beta hydroxy acid) or glycolic acid (an alpha hydroxy acid), combined with regular cleansing, effectively remove oxidized lipids, pollutants, and debris from the skin's surface. This reduces the risk of oxidative stess and helps prevent pore congestion and reduces acne risk [14]. However, overcleansing or excessive exfoliation should be avoided—not due to the debunked "rebound sebum production" myth, however because these practices can compromise the stratum corneum's barrier function, increasing transepidermal water loss (TEWL) and irritation potential.
4. Sun protection: Exposure to UV and Visible Light light generates reactive oxygen species (ROS) and on top initiate lipid peroxidation in sebum, leading to the formation of lipid hydroperoxides and other oxidized lipids that can disrupt skin barrier function and promote inflammation [10]. The daily use of broad-spectrum sunscreen protects against UV and VL-induced oxidative stress which contribute to lipid peroxidation [7]. Sunscreens containing antioxidants (like Licochalcone A) can provide additional protection. Sunscreen efficacy directly correlates with reduced UV-induced lipid peroxidation.
5. Healthy diet: Consuming a diet rich in omega-3 fatty acids, fruits, and vegetables can enhance the skin's antioxidant defenses and reduce inflammation associated with lipid peroxidation [6].
6. Avoiding environmental stressors: Reducing exposure to pollutants and smoking can minimize oxidative stress on the skin. ​

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7. Sebum regulating topical ingredients: There are several evidence based skin care ingredients. I will highlight one called L-Carnitine. L-Carnitine is a skin’s own amino acid derivative is produced from the amino acids lysine and methionine. It supports sebum regulation through several mechanisms:             
​▌Increased β-oxidation (“fat burning”): L-carnitine significantly augments β-oxidation in human sebocytes, which is the process by which fatty acids are broken down [23]. This leads to a decrease in intracellular lipid content.
▌Sebum secretion reduction: Topical application of a 2% L-carnitine formulation for 3 weeks significantly decreased the sebum secretion [23].
▌Bio-availability: Topically applied L-carnitine is bioavailable and can reach the dermis, allowing it to interact with sebaceous glands [23].
New in vitro data shows 86% sebum reduction for even a low concentration of L-carnitine [24].

8. Mattifying oil absorption: Mattifying agents formulated for oily skin work by absorbing excess sebum and reducing shine through ingredients like clays, silica, and polymers (like starch). Overuse can lead to product buildup, potentially trapping impurities on the skin's surface.
9. Blotting papers are thin, absorbent sheets designed to absorb thus remove excess oil from the skin's surface, providing a temporary matte appearance [25].

Always consult a qualified healthcare professional to determine what the most suitable approach is for your skin health and beauty.
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Take care
Anne-Marie
  
[1] Ayala et al. Oxid Med Cell Longev. 2014;360438.
[2] Endale et al. Front Cell Dev Biol. 2023;11:1226044. 
[3] Su et al. Oxid Med Cell Longev. 2019;5080843.
[4] Cao et al. Front Physiol. 2022;13:921866.
[5] Sinclair et al. Nat Commun. 2021;12:1592.
[6] Briganti & Picardo (2003) J Eur Acad Dermatol Venereol. 17(6):663-9
[7] Niki (2015) Free Radic Res. 49(7):827-34
[8] Wong A, et al. J Clin Dermatol Ther. 2016;3(1):020.
[9] Gruber F, et al. Front Endocrinol. 2020;11:607076. 
[10] Picardo et al. (2009) Dermatoendocrinol. 1(2):68-71  (was 5)
[11] Kostyuk V, et al. PLoS One. 2012;7(8):e44472. 
[12] Briganti & Picardo (2003) J Eur Acad Dermatol Venereol. 17(6):663-9
[13] Ottaviani et al. (2006) J Invest Dermatol. 126:2430-2437
[14] Bowe & Logan (2010) Lipids Health Dis. 9:141
[15] Yadav et al. (2019) Sci Rep. 9:4496
[16] Tang, D. et al. (2021) Cell Res 31, 107–125. 
[17] Veeckmans, G. et al. (2023) The FEBS Journal.
[18] Li, J. et al. (2020) Cell Death Dis. 11, 88.
[19] Feng et al. (2023) Mol. Biomed. 4, 33.
[20] Kim et al. (2005) J Invest Dermatol. 125(5):1009-16
[21] Huang et al. (2013) Mol Med Rep. 7(6):1977-82
[22] Bocheva et al. (2022) Int J Mol Sci. 23:1238
[23] Peirano et al. (2012) J Cosmet Dermatol. 11(1):30-36
[24] BDF data on file Dr. Dorothea Schweiger
[25] Wu et al. (2019) J Food Drug Anal. 27(2):610-61

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