You might know that usually you shouldn’t mix tretinoin (all-trans retinoic acid) and benzoyl peroxide. Benzoyl peroxide is an effective acne treatment and works against acne-causing bacteria by oxidizing them.
A major benefit of benzoyl peroxide is that it is unlikely to cause bacterial resistance. It may even reduce the risk of bacterial resistance to topical antibiotics when used alongside them¹. However, the oxidizing action of benzoyl peroxide is indiscriminate and can cause tretinoin to breakdown – likely along its tail where there are many sensitive carbon double bonds.
Why might someone want to use tretinoin and benzoyl peroxide together? The combination is sometimes suggested by dermatologists⁴ and is effective² – if irritation is kept in check.
In a clinical trial³, the combination was shown to reduce acne faster and more effectively than each one alone. The two ingredients have some different effects on the skin, which may work together to give better results.
Experiments have found that mixing benzoyl peroxide with tretinoin can quickly lead to degradation – especially when they are exposed to light, with and without UV. While conditions were different in each experiment, within 24 hours of mixing and light exposure more than 80% of the tretinoin had degraded⁵⋅⁶. In one experiment, 50% of the tretinoin had degraded within 2 hours⁶.
Because of this information, it is often recommended to use one in the morning and the other in the evening.
In one of these experiments⁶, adapalene was found to be stable against benzoyl peroxide’s oxidizing action and is often used as a substitute for tretinoin.
While this experimental evidence is convincing, other experiments suggest stability. Two experiments⁵⋅⁷ with tretinoin encapsulated in microspheres (Retin-A Micro), found that about 95% of the tretinoin remained after 8 hours of mixing with benzoyl peroxide and exposure to non-UV light. When exposed to UV light, about 80% of the tretinoin remained after 6 hours⁷. An experiment⁸ with tretinoin that wasn’t encapsulated (Atralin Gel) also showed stability when mixed with 5% benzoyl peroxide. After 7 hours storage in an amber glass vial at 32ºC there was no degradation of the tretinoin.
Retin-A Micro’s encapsulation of tretinoin inside cross-polymer microspheres seems to have reduced the breakdown of it by benzoyl peroxide. This is most likely by physically separating the ingredients and reducing their ability to interact.
The second formula didn’t use encapsulation, but also had minimal-to-no degradation of the tretinoin. What stands out to me about the Atralin Gel is the butylated hydroxytoluene (BHT), an antioxidant commonly used in pharmaceuticals and food. Many other formulas of tretinoin have BHT, but it’s difficult to say whether they will also be stable when mixed with benzoyl peroxide. Only the Atralin Gel formula was tested.
These experiments show that the formulation of tretinoin largely determines how stable it is when mixed with benzoyl peroxide and exposed to light. There are differences between formulas available on the market, so a flat-out rule of “never mix” is likely false. This seems to be backed up by clinical reports of the combination of tretinoin and benzoyl peroxide being effective – as well as the experiments showing stability.
Twyneo is a new prescription that conveniently combines tretinoin encapsulated in silica core shells and benzoyl peroxide in the same formula. It has been shown to be stable⁹. Adapalene is an alternative retinoid that is stable against benzoyl peroxide. Differin and other brands of adapalene are available over the counter in the United States.
For people without access to these formulas, those with encapsulated tretinoin like Retin-A Micro and an antioxidant like in Atralin Gel may help put the combination of tretinoin and benzoyl peroxide back on the table.
Talk to your dermatologist or doctor!
- The Role of Benzoyl Peroxide in the New Treatment Paradigm for Acne
- Retinoic acid cream (Airol cream) and benzoyl-peroxide in the treatment of acne vulgaris
- Case-based experience with the simultaneous use of a fixed topical antibiotic/benzoyl peroxide combination and a topical retinoid in the optimization of acne management
- The stability of tretinoin in tretinoin gel microsphere 0.1%
- Chemical stability of adapalene and tretinoin when combined with benzoyl peroxide in presence and in absence of visible light and ultraviolet radiation
- The effect of simulated solar UV irradiation on tretinoin in tretinoin gel microsphere 0.1% and tretinoin gel 0.025%
- Absence of Degradation of Tretinoin When Benzoyl Peroxide is Combined with an Optimized Formulation of Tretinoin Gel (0.05%)
- Twyneo® (Microencapsulated Benzoyl Peroxide 3%, Tretinoin 0.1%) Phase 3 Efficacy and Safety: Results From Two Randomized Controlled Clinical Trial