What should we know about benzoyl peroxide?

Benzoyl peroxide (C6H5CO)2O2 is a chemical compound from the organic peroxides family, characterised by the presence of a peroxide group (-O-O-) within its structure. Benzoyl peroxide is primarily used in the polymer industry to initiate polymerisation reactions. It also serves to harden polyester resins and silicone rubbers, and to strengthen fibreglass-based composites. It is also used in the food industry for the bleaching of flours, cheeses, vegetable oils, and fats. However, it is most widely used on the skin, due to its ability to act on acne.

The benzoyl peroxide is available in various forms, concentrations, and combinations to manage acne. The formulations vary according to the skin's needs: cleansers, creams, lotions, and masks are suitable for mild to moderate acne, while more concentrated gels and serums are recommended for more severe forms of acne. It can be found over-the-counter in low concentrations (2% to 5%), suitable for cases of mild to moderate acne. However, for more severe acne, products with a higher concentration (10%) or in combination with other treatments, such as antibiotics (erythromycin, clindamycin) or retinoids (adapalene), may be prescribed by a doctor. Furthermore, the benzoyl peroxide can be combined with active ingredients, such as niacinamide, to reduce the skin dryness it induces.

The technique that allows the synthesis of benzoyl peroxide unfolds in 3 major stages. This process includes a Grignard reaction which causes bromobenzene to react with magnesium in the presence of an anhydrous solvent, often ether, to form phenylmagnesium bromide, also known as Grignard reagent. This then reacts with carbon dioxide (CO₂), leading to the formation of a carboxylate salt. The addition of hydrochloric acid (HCl) releases benzoic acid (2) in the form of a crystallised solid.

Benzoic acid reacts with thionyl chloride (SOCl₂) to form benzoyl chloride (3). This step involves the substitution of the hydroxyl (-OH) group in the acid with a chlorine atom, generating a more reactive acid derivative, benzoyl chloride (3). This then reacts with hydrogen peroxide (H₂O₂) in the presence of a base (NaOH). This reaction results in the formation of benzoyl peroxide (1) through the interaction of the two acyl (C=O) groups with the peroxide oxygen (-O-O-).

The benzoyl peroxide displays several properties that make it a versatile active ingredient in the management of acne. It is recognised for its antibacterial, sebostatic, keratolytic and anti-inflammatory effects, thus effectively reducing blemishes. Moreover, these properties could also be beneficial in the management of folliculitis and seborrheic dermatitis. Finally, when combined with retinoids such as adapalene, benzoyl peroxide would help to decrease the appearance of acne scars, by promoting cell renewal and preventing inflammation.

• Benzoyl Peroxide: An antibacterial agent.

  When applied to the skin, benzoyl peroxide breaks down into benzoic acid while releasing reactive oxygen species (ROS). These highly reactive molecules attack the DNA and proteins of Cutibacterium acnes, the bacteria responsible for acne, thereby eliminating them.

• Benzoyl peroxide is an anti-inflammatory.

  Benzoyl peroxide is primarily known for its antibacterial properties, but it also exhibits indirect anti-inflammatory effects. By eliminating bacteria Cutibacterium acnes, which are responsible for acne, it reduces the inflammatory response these bacteria trigger in the skin. Its ability to decrease the factors that trigger inflammation gives it an indirect beneficial effect on redness and irritation.

• Benzoyl peroxide possesses a sebostatic property.

  Benzoyl peroxide also has a direct sebostatic action and works to reduce the stimulation of the sebaceous glands. This property is particularly beneficial for individuals with oily skin as it helps to keep the amount of sebum synthesis under control.

• Benzoyl peroxide has a keratolytic action.

  Hyperkeratinisation is one of the symptoms of acne. It manifests as an excessive production of keratin that accumulates in the follicles, leading to a thickening of the stratum corneum. Benzoyl peroxide plays an exfoliating role due to specific molecules dissociated from benzoyl peroxide during its application, such as the benzoyl radical and reactive oxygen species. These unstable molecules then split to form carbon dioxide which promotes cellular renewal by stimulating the detachment of dead cells from the skin surface.

The use of benzoyl peroxide in skincare requires certain precautions due to its potential adverse effects.

Benzoyl peroxide can cause skin reactions similar to burns upon application. This risk can be heightened by a high concentration of benzoyl peroxide and by applying the product in excessive amounts. Furthermore, the application of benzoyl peroxide can lead to risks of discolouration of hair and clothing if they come into direct contact with the product. Therefore, it is advised to apply it in the evening with hair tied back and to wait half an hour before going to bed, to avoid discolouring bed sheets. Moreover, benzoyl peroxide is not recommended for pregnant women and children under the age of 12.

Furthermore, benzoyl peroxide is potentially phototoxic and can increase the skin's sensitivity to sunlight. Indeed, when exposed to UV rays, reactive oxygen species (ROS) are produced. The oxidative stress caused by ROS damages DNA, lipids, and proteins, thus affecting the health of skin tissues. This reaction results in adverse effects such as red patches, burns similar to sunburn, erythema or hyperpigmentation. This is why benzoyl peroxide is preferably applied in the evening. Sun protection is then necessary the following day.

• CIVATTE J. & al. Research in humans on the phototoxic power of 5% benzoyl peroxide. Dermatologica (1983).

• CIVATTE J. & al. Predicting benzoyl peroxide phototoxicity through photoepidermotests after multiple applications. The preventive potential of a UVB filter. National Centre for Biotechnology Information (1988).

• SHARON F. & et al. The effectiveness and safety of a combined benzoyl peroxide/clindamycin topical gel compared to benzoyl peroxide on its own and a benzoyl peroxide/erythromycin combination product. Journal of Cutaneous Medicine and Surgery (2001).

• VIDAL. Active substance benzoyl peroxide (2013)

• ERTUGRUL H. Acne vulgaris. National Centre for Biotechnology Information (2014).

• MARTEL. P. & al. Efficacy of Adapalene and Benzoyl Peroxide in the treatment of acne lesions and scars. Journal of Dermatological Science (2015).

• ZHANG Q. & al. Topical Benzoyl Peroxide for Acne. Cochrane Library (2020).

• LUN HON K. & al. Dermatology: how to manage acne vulgaris. National Centre for Biotechnology Information (2021).

• FRITSCH P. & al. Topical Combination Products for Facial Acne. National Library of Medicine (2022).

• DEHGHAN D. & al. New topical drug delivery systems in acne treatment: Understanding the molecular mechanisms and the role of targeted delivery systems for improved therapeutic results. Journal of Drug Delivery Science and Technology (2022).

• GOODMAN B. & et al. Benzoyl Peroxide. National Centre for Biotechnology Information (2024).