Benzoyl peroxide is an active ingredient primarily used to treat acne due to its antibacterial, anti-inflammatory, keratolytic, and sebostatic properties. These effects make it a widely recommended product for combating this issue. Combining benzoyl peroxide with other active ingredients can enhance its effectiveness and reduce its side effects. So, what are these active ingredient combinations, and what benefits do they provide in synergy with benzoyl peroxide?
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Can benzoyl peroxide be used with other active ingredients?
Summary
- Association #1: Benzoyl Peroxide and Retinoids
- Association #2: Benzoyl Peroxide and Antibiotics
- Association #3: Benzoyl Peroxide and Niacinamide
- Sources
Published January 27, 2025,
updated on January 27, 2025,
by
Lilia, Scientific Editor
—
10 min read
Association #1: Benzoyl Peroxide and Retinoids.
Topical retinoids , derivatives of vitamin A, are commonly used in the treatment of acne. They promote the peeling of the follicular epithelium, thus preventing the formation of new comedones. In addition, retinoids facilitate the penetration of other active ingredients into the hair follicle, thereby optimizing the effectiveness of combined treatments.
Benzoyl Peroxide and Adapalene.
The combination of adapalene and benzoyl peroxide in a single product is commonly used for the topical treatment of acne, particularly for moderate to severe forms. Adapalene, a topical retinoid, regulates cell renewal and limits pore obstruction, thus reducing the formation of comedones. Benzoyl peroxide, on the other hand, is a powerful antibacterial that targets Cutibacterium acnes, the bacteria involved in the development of acne.
This combination also promotes cellular regeneration and can reduce the risk of scarring. A multicenter study (OSCAR) involving 503 patients demonstrated that, over 24 weeks, the combined treatment of adapalene - benzoyl peroxide significantly reduced the number of acne lesions compared to the placebo. The reduction of lesions also led to a decrease in the risk of atrophic scars: by the 24th week, 32.9% of the treated areas showed little or no scarring compared to 16.4% for the placebo group, according to the global evaluation of scars.
Benzoyl peroxide and retinol.
The retinol, a form of retinoid available over-the-counter, is widely used for its proven effectiveness in reducing the expression of matrix metalloproteinases, enhancing collagen synthesis, as well as increasing hyaluronic acid, elastin production, and epidermal cell renewal. When combined with other active ingredients, it can act on several pathways involved in the formation of acne, thus providing better results.
A 12-week study, conducted on 33 subjects with mild to moderate acne, evaluated the effectiveness of a routine combining a low-dose topical application of benzoyl peroxide (2.5%) in the morning and retinol in the evening. The results show a significant improvement in acne severity with a reduction in both inflammatory and non-inflammatory lesions. The treatment also significantly improved parameters such as skin texture, skin tone uniformity, and residual spots.
The benzoyl peroxide and retinol should not be used simultaneously as they risk causing irritations.
Association #2: Benzoyl Peroxide and Antibiotics.
Certain antibiotics are widely used in the treatment of moderate to severe acne. However, they are likely to cause a bacterial resistance within the skin flora. The combination of antibiotics with benzoyl peroxide not only enhances the product's effectiveness but also reduces the risk of bacterial resistance on the skin. This is because benzoyl peroxide rapidly decreases the presence of bacteria, thereby limiting their exposure to antibiotics.
Benzoyl peroxide and erythromycin.
The combination of erythromycin and benzoyl peroxide is used in the topical treatment of moderate to severe acne. Erythromycin, an antibiotic, inhibits the growth of Cutibacterium acnes on the skin surface, which leads to a reduction in the concentration of free fatty acids in the sebum responsible for skin inflammation. By combining this antibiotic with benzoyl peroxide in a single product, the development of bacterial resistance is limited and the effectiveness of the treatment is enhanced. Various studies have demonstrated the usefulness of the combination of 3% erythromycin and 5% benzoyl peroxide for the topical treatment of acne, including a study conducted on 165 patients over twelve weeks. The results showed that the erythromycin and benzoyl peroxide combination is significantly more effective from the second week onwards, than benzoyl peroxide alone or erythromycin alone.
Benzoyl peroxide and clindamycin.
The combination of benzoyl peroxide and clindamycin is another commonly used option in the topical treatment of moderate to severe acne. Clindamycin is a topical antibiotic that targets the bacteria responsible for acne, but with a mechanism different from that of benzoyl peroxide.
Indeed, it restricts bacterial proliferation by blocking the synthesis of bacterial proteins, while benzoyl peroxide works by producing reactive oxygen species that interact with bacterial proteins by oxidizing them, which disrupts their survival and functions. Together, these two ingredients offer a dual effect: benzoyl peroxide directly combats bacteria and reduces the risks of bacterial resistance, while clindamycin limits inflammation and skin eruptions.
A study conducted on 2813 patients over a 12-week period evaluated the effectiveness of a daily administered combination of benzoyl peroxide (2.5%) and clindamycin (1.2%), compared to each substance used individually or to the vehicle. There was an improvement in acne reduction of 28.6% for the combination of the two products, versus 21.9% for clindamycin alone and 21% for benzoyl peroxide alone.
Comparison of the effectiveness between the combination of benzoyl peroxide and clindamycin versus the individual products on acne.
Source: CHEN D. & al. An aqueous gel fixed combination of clindamycin phosphate 1.2% and benzoyl peroxide 2.5% for the once-daily treatment of moderate to severe acne vulgaris: assessment of efficacy and safety in 2813 patients. National Center for Biotechnology Information (2008).
Association #3: Benzoyl Peroxide and Niacinamide.
Although highly effective, the benzoyl peroxide can sometimes cause side effects such as irritations or skin dryness. To overcome these limitations, it is increasingly common to combine it with other active ingredients that complement and enhance its action, while reducing the risk of irritation.
Benzoyl peroxide and niacinamide in the same product could exert complementary and synergistic effects, enhancing the effectiveness in the topical treatment of acne. A 28-day pilot trial on 22 patients suffering from mild to moderate acne aimed to evaluate this effectiveness. The results showed a significant decrease in acne lesions after treatment compared to the vehicle. Non-inflammatory, inflammatory, and total lesions decreased by 40%, 43%, and 41% respectively. Additionally, skin redness decreased by 11% after treatment and sebum production by 42%.
Furthermore, benzoyl peroxide is not always well tolerated, particularly during the initial weeks, causing irritation, erythema, and skin dryness by interfering with the skin barrier, leading to an increase of up to 80% in transepidermal water loss. This is where niacinamide, an anti-inflammatory molecule, comes into play. It is capable of preserving the function of the skin barrier by reducing transepidermal water loss, which allows epidermal cells to improve the epidermis barrier and the level of hydration.
This study, however, must be interpreted with caution, as the number of subjects is not significant enough to yield reliable results.
| Benzoyl Peroxide Alone | Niacinamide Alone | Benzoyl Peroxide and Niacinamide | |
|---|---|---|---|
| Antibacterial Action | ++ | +++ | |
| Reduction of Sebum Production | ++ | ||
| Anti-inflammatory Activity | ++ | ++ | |
| Comedolytic and Keratolytic Activity | ++ | ++ | |
| Potential use for inflammatory acne | ++ | +++ | |
| Potential use for inflammatory rosacea | NO | YES | YES |
| Alteration of the Skin Barrier | YES | NO | NO |
Comparative chart of the combination of benzoyl peroxide and niacinamide in acne and rosacea compared to the individual components.
Source: COLOMBO F. & al. The Logic Behind a Fixed Combination of Benzoyl Peroxide and Niacinamide in the Treatment of Acne Vulgaris: A Narrative Review. Dermatology Journal of Cosmetic and Laser Therapy (2024).
Sources
SWANN. R.W. & al. A double-blind study on the efficacy of a combination of 3% erythromycin and 5% benzoyl peroxide in the treatment of acne vulgaris. Journal of the American Academy of Dermatology (1983)
PIERARD G. E. Benzamycin, an update on the topical treatment of acne. CHU-Department of Dermatopathology (1997).
CHEN D. & al. An aqueous gel fixed combination of clindamycin phosphate 1.2% and benzoyl peroxide 2.5% for the once-daily treatment of moderate to severe acne vulgaris: evaluation of effectiveness and safety in 2813 patients. National Center for Biotechnology Information (2008).
POPP. K.F. & others. A Current Review of Topical Benzoyl Peroxide: New Perspectives on Formulation and Utilization. Dermatologic Clinics (2009).
MARTEL P. & al. Effect of the fixed combination adapalene-benzoyl peroxide on acne scars: results of a multicenter, randomized, half-face, single-blind, vehicle-controlled study. Annals of Dermatology and Venereology. (2015)
HELFRISH Y. R. & et al. Treatment of Acne in Pregnancy. The Journal of the American Board of Family Medicine (2016).
Bausch Health, Canada Inc. & al. BENZAMYCIN- Erythromycin and Benzoyl Peroxide Topical Gel, USP (2020).
ATILLASOY E. & et al. A Topical Combination Regimen of Benzoyl Peroxide and Retinol Moisturizer for Mild to Moderate Acne. Journal of Drugs in Dermatology (2022).
COLOMBO F. & others. The Logic Behind a Fixed Combination of Benzoyl Peroxide and Niacinamide in the Treatment of Acne Vulgaris: A Narrative Review. Dermatology Journal of Cosmetic and Laser Therapy (2024).
EISENDLE K. & al. Efficacy and Skin Microbiome Modulation Effects of a Fixed-Concentration Combination of Benzoyl Peroxide 4% Plus Niacinamide 4% in a Film-Forming Cream in Subjects with Mild-to-Moderate Acne: A Non-Sponsored, Prospective, Assessor-Blinded, Pilot Trial. Cosmetics (2024)
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