Cosmeceutical Critique: Benzoyl peroxide


Benzoyl peroxide (BPO) has been used for more than 45 years for the treatment of acne, and has recently been enjoying renewed popularity, thanks to its performance in recent studies of both prescription and over-the-counter formulations (J. Drugs Dermatol. 2013;12:180-5). In fact, BPO is one of the two most common ingredients in OTC acne products (Semin. Cutan. Med. Surg. 2008;27:170-6). The prescription form is used alone or in combination with tretinoin, adapalene, or clindamycin. BPO, originally sourced from the coal tar component chlorhydroxyquinoline, is now typically prepared by treating hydrogen peroxide with benzoyl chloride (Dermatol. Clin. 2009;27:17-24). Because it can generate reactive oxygen species and commonly leads to skin irritation, its use is somewhat limited.

Antibacterial uses

BPO imparts bactericidal activity by releasing highly reactive oxygen (free radicals) that can oxidize proteins in bacterial cell membranes. It also exhibits antibacterial action against Propionibacterium acnes and Corynebacterium acnes, the bacteria implicated in the pathophysiology of acne (Dermatol. Ther. 2012;25:6-11), as well as Staphylococcus capitis, S. epidermis, S. hominis, P. avidum, P. granulosum, and the yeast Pityrosporum ovale (J. Appl. Bacteriol. 1983;54:379-82).


Many studies over the years have shown that topically applied BPO effectively treats acne (Expert Opin. Pharmacother. 2009;10:2555-62). These ameliorative results, which include enhancing the benefits of other topical antimicrobials, are thought to arise because BPO, a highly lipophilic molecule, penetrates through the sebum and into the pilosebaceous unit, and exerts bactericidal, keratolytic, and anti-inflammatory activity (Skin Pharmacol. Physiol. 2006;19:283-9). BPO may contribute to the antiacne efficacy of other antimicrobials by preventing bacterial resistance and promoting penetration into the sebum, keratin, and polysaccharides to reach the target bacteria. Specifically, the oxidative activity of BPO helps eliminate the biofilm polysaccharides secreted by P. acnes, thus expediting the delivery of other agents to the bacteria (Int. J. Dermatol. 2006;45:872; Int. J. Dermatol. 2003;42:925-7).

Not surprisingly, several studies have shown that the antiacne efficacy of a combination of BPO with other antimicrobials, such as clindamycin, is greater than that of either agent used alone. Simpson et al. demonstrated that the use of clindamycin and BPO together led to a 61% decline in inflammatory lesions after 3 months, as compared with 39% and 35%, respectively, when the agents were used alone (J. Am. Acad. Dermatol. 1997;37:590-5). BPO is frequently paired with salicylic acid to treat acne (Clin. Exp. Dermatol. 2011;36:840-3).

Acne often improves more rapidly with BPO treatment than with retinoids and other acne therapies, and data suggest that the faster clearing of acne lesions and comedones is most likely because of its keratolytic activity (Dermatol. Clin. 2009;27:17-24; J. Dermatolog. Treat. 2003;14:166-71). However, the dryness and irritation associated with BPO usage may undermine patient compliance. Several studies have suggested that BPO is effective in cleanser formulations, which seem to reduce irritation (Clin. Exp. Dermatol. 2011;36:840-3).


Reports that BPO predisposed mice to skin cancer, particularly when they were exposed to ultraviolet radiation, prompted the Food and Drug Administration to form an advisory committee in 1992 to review the safety of BPO. The committee called for additional photocarcinogenicity studies while suggesting that BPO products include animal safety data on the labels. BPO-containing acne products were kept on the market. In the ensuing two decades, newer safety studies have led the FDA to change the classification of BPO to category I, deeming the OTC topical treatment of acne to be generally recognized as safe and effective (GRASE) (Fed. Regist. 2010;75:9767-77).


When BPO breaks down into benzoic acid in the skin, benzoyloxy, a free radical, forms as an intermediate (Prog. Clin. Biol. Res. 1995;391:245). Benzoyloxy can decarboxylate into a phenyl radical. These free radicals produce oxidative stress, which may cause DNA strand breaks in keratinocytes or may harm proteins or lipids. In addition to becoming a free radical, BPO depletes membrane and cytosolic antioxidants (Toxicology 2001;165:225-34). No retrospective trials looking at the effects of long-term use of BP on photoaging have been performed, so the role of BPO in photoaging is not clear. One study in mice found that topical BP has some of the same effects on skin as UVB (J. Invest. Dermatol. 1999;112:933-38).

Other safety issues

Acne is not uncommon among pregnant women. Although safety studies of BPO use by pregnant women have not been performed, various authors suggest that only about 5% of topically applied BPO is absorbed systemically, implying that topical BPO can be safely used during pregnancy (Int. J. Dermatol. 2002;41:197-203; Can. Fam. Physician 2011;57:665-7; Drugs 2013;73:779-87; Dermatol. Ther. 2013;26:302-11).

In approximately 1% of patients, topical BPO causes contact or irritant dermatitis (Contact Dermatitis 1999;41:233; Contact Dermatitis 1996;34:68-9). The use of barrier repair moisturizers may reduce the incidence of irritation, though this has not been proven.


Recommended Reading

Laser settings tested against melasma
MDedge Dermatology
Pyoderma Gangrenosum Following Gastric Bypass Surgery
MDedge Dermatology
Gold-coated microparticles aid acne treatment
MDedge Dermatology
Cosmetic Corner: Dermatologists Weigh in on Antiperspirants
MDedge Dermatology
VIDEO: Spruce up your suturing; try these techniques
MDedge Dermatology