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!

Sources:

1. The Role of Benzoyl Peroxide in the New Treatment Paradigm for Acne
2. Retinoic acid cream (Airol cream) and benzoyl-peroxide in the treatment of acne vulgaris
3. 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
4. The stability of tretinoin in tretinoin gel microsphere 0.1%
5. Chemical stability of adapalene and tretinoin when combined with benzoyl peroxide in presence and in absence of visible light and ultraviolet radiation
6. The effect of simulated solar UV irradiation on tretinoin in tretinoin gel microsphere 0.1% and tretinoin gel 0.025%
7. Absence of Degradation of Tretinoin When Benzoyl Peroxide is Combined with an Optimized Formulation of Tretinoin Gel (0.05%)
8. Twyneo® (Microencapsulated Benzoyl Peroxide 3%, Tretinoin 0.1%) Phase 3 Efficacy and Safety: Results From Two Randomized Controlled Clinical Trial

"Can you mix tretinoin and benzoyl peroxide?" on KindofStephen.

“Fungal acne” often refers to the idea that a person who has not seen improvement in their acne from conventional treatments is actually suffering from acne caused by fungus. The fungus is often identified as the genus Malassezia, formerly called Pityrosporum.⁣

Fungal (or yeast, a type of fungus) infections of the skin can occur. Malassezia fungus can cause small red bumps or white-headed pimples on the skin. It might look a lot like acne, but it’s not acne. It’s a condition called malassezia or fungal folliculitis.

It’s described as acneiform, which means “looks like acne” but it isn’t acne.

Proponents of “fungal acne” will often recommend changing the products a person uses to being free of ingredients that supposedly feed fungus. This is akin to “detoxifying” and is a common trope in pseudoscience.⁣ Many of these “not fungal acne safe” ingredients also happen to overlap with acne triggers.

There’s little to no human evidence that removing the often highlighted ingredients will have benefits against fungal infections of the skin. The evidence given is often from cell culture studies, anecdotal, or taken out of context.⁣

A story shared by a Redditor highlights why self-diagnosing “fungal acne” can be dangerous. This Redditor self-diagnosed what they thought was “fungal acne” and went on a “skincare detox”. The infection continued to reoccur. Finally, after visiting a doctor, and a skin swab…it was confirmed to be a staph infection. This means during this time the Redditor was self-treating their “fungal acne”, they were letting a potentially dangerous staph infection go untreated.⁣

Fungal folliculitis can be identified by doctors through tests, their training, and experience. If the infection is confirmed to be fungal folliculitis, treatment often involves topical (or in severe cases systemic) antifungal medication.⁣

⁣It’s important to get a proper diagnosis, so the proper treatment can be given.⁣ It’s important not to self-diagnose. There are many conditions that can look like acne or how “fungal acne” is described, but can be harmful if left untreated.⁣

I’ve seen some experts use the term “fungal acne” colloquially online. We don’t need to simplify the terminology we use. We’re capable of using complex words like niacinamide or emulsification.

Call it by its name. Fungal folliculitis.

But only after a diagnosis is made.

"It’s Not Fungal Acne" on KindofStephen.

Atrophic scarring is caused by a loss of tissue, so they can appear as sunken areas in the skin or even as holes, commonly referred to as ‘ice pick’ scars.

There were three experiments in total, a pilot study with 20 participants that compared Adapalene 0.3% gel compared to a control vehicle, another pilot study with 31 participants comparing Adapalene 0.1% and Benzoyl Peroxide 2.5% gel with a control vehicle, and a larger study with 54 participants comparing Adapalene 0.3% and Benzoyl Peroxide 2.5% gel with a control vehicle.

All three experiments were pre-registered on ClinicalTrials.gov which helps reduce reporting bias. Often there is no incentive or reason to report on data from an experiment if there is no effect.

I’m going to focus on the latter paper as it has the most statistical power (> 80%) and the most clinically relevant results.

In brief, the experiment using Adapalene 0.1% with Benzoyl Peroxide 2.5% gel showed no change in the amount of atrophic scarring after 6 months of treatment, but people using the vehicle control saw an increase in scars (about 2 more scars after 6 months).

In the pilot study with Adapalene 0.3%, participants and investigators saw an improvement in scarring assessments at Week 1 and Week 24.

All three studies found a clinically relevant and statistically significant reduction in acne lesions for those using any Adapalene based gels.

With the Adapalene 0.3% with Benzoyl Peroxide 2.5% gel study, there was a statistically significant improvement in the scar assessment as early as Week 1.

By the end of the experiment at Week 25, there was a 15.5% decrease in a validated scar assessment scale – this worked out to about a mean decrease of 2 acne scars per half of the face.

Participants applied the Adapalene gel to only half of the face and the vehicle control on the other half, the researchers believe that if participants had applied the Adapalene gel to the whole face, there would be a decrease of a mean of about 4 acne scars for the entire face.

For the vehicle control side that contained no Adapalene, participants saw an increase of about 1.5 acne scars at the end of 24 weeks.

In terms of non-validated assessments, the amount of patients who responded to “How visible are the indents or holes to you?” with “A little visible” increased from 37.5% at Week 1 to 62.1% at Week 24.

Because some atrophic scarring can resolve on its own, the researchers believed the decrease in scarring with the Adapalene 0.3% and Benzoyl Peroxide 2.5% gel could be due to an increase in the speed of this resolution. For older scars, they believe that the Adapalene gel could be due to remodelling the dermis of the skin (possibly through stimulation of procollagen), improving their appearance.

Another factor would be the reduction in inflammatory acne lesions which could lead to new atrophic scarring formation.

The researchers point out that scar improvement was seen past 3 months, and that people using Adapalene may consider using the product for longer than 6 adapalene to help improve and prevent the appearance of atrophic scarring

In the US, Adapalene is now available over-the-counter as Differin with Adapalene at 0.1%. If you have moderate-to-severe acne with atrophic scarring you may consider speaking to your doctor and getting a prescription for the stronger 0.3%.

In terms of other retinoids, the researchers point out that there isn’t much research on topical use and improvement in atrophic scarring. For tretinoin I did find two studies, but they included other interventions in combination with the tretinoin. One used iontophoresis to enhance the penetration of tretinoin, and another used tretinoin in combination with microneedling. Both studies found improvement in atrophic scarring. Adapalene and other retinoids activate some of the same receptors, and since topical use of tretinoin has shown to increase procollagen as well, it’s likely that it will provide improvement on atrophic scarring as well.

B. Dreno, J. Tan, M. Rivier, P. Martel, R. Bissonnette, Adapalene 0.1%/benzoyl peroxide 2.5% gel reduces the risk
of atrophic scar formation in moderate inflammatory acne:
a split-face randomized controlled trial, Journal of the European Academy of Dermatology and Venereology (2016), DOI: 10.1111/jdv.14026

M.J. Loss, S. Leung, A. Chien, N. Kerrouche, A.H. Fischer, S. Kang, Adapalene 0.3% gel shows efficacy for the treatment of atrophic acne scars, Dermatology and Therapy (2018), DOI: 10.1007/s13555-018-0231-8

B. Dréno, R. Bissonnette, A. Gagné-Henley, B. Barankin, C. Lynde, N. Kerrouche, J. Tan, Prevention and reduction of atrophic acne scars with adapalene 0.3%/Benzoyl peroxide 2.5% gel in subjects with moderate or severe facial acne: Results of a 6-month randomized, vehicle-controlled trial using intra-individual comparison, American Journal of Clinical Dermatology (2018), DOI: 10.1007/s40257-018-0352-y

"Adapalene 0.3% may help improve the appearance of atrophic acne scars" on KindofStephen.

"Galderma Announces FDA Approval of 0.1% Differin® Gel For Over-the-Counter Acne Use" on KindofStephen.

"Using Bacteria’s Own Antibacterial Systems Against Them Could Lead To Targeted, Safer Antibiotics" on KindofStephen.

Previous research has shown that comedones have a cyclical nature, either forming into inflammatory acne, re-appearing, or resolving.

Based on clinical experience, this cycle was estimated to take between 2-6 weeks. However, no studies had been done that provided direct evidence for this timeline.

A week after the comedone was extracted the skin appeared to resolve – to the naked eye. Under a microscope, however, researchers found that dead skin cells and sebum were already beginning to accumulate and reform the comedone.

This highlights the importance of continuing acne treatment even after the skin looks like it has cleared. This may also provide evidence for the use of acne treatments over the entire face or affected area instead of spot treating.

Further research with this technique could show how acne treatments prevent this comedone reformation, if there is individual variation on this reformation, what changes in the skin cells is causing the excess build up, and how long a lesion needs to be treated before the pore returns to normal.

"In vivo study of comedone reformation" on KindofStephen.

This paper found a correlation between the time that female subjects went to sleep and how much sebum their skin produced.

A slight increase in sebum production was seen the later they went to sleep. As well, sleeping less was correlated with a slight decrease in sebum production. This relationship wasn’t seen in the male participants of the study.

They also found a correlation between levels of free testosterone and 5α-reductase (an enzyme that converts testosterone in to dihydrotestosterone – a more active form).

Curiously this correlation was, again, only significant for women – despite men having 10 times more free testosterone than women. The researchers think that there may be a maximum threshold for how much testosterone can influence sebum production. There’s also research indicating that the sebaceous gland’s sensitivity to testosterone varies among individuals as well.

While the study’s sample size was quite small, and it’s completely possible this isn’t reproducible, due to random chance or some other variable…there is newer research describing a pathway between inflammation and sebum production – which may be what’s at play here.

"Study finds link between sleep times and sebum production of women’s skin" on KindofStephen.

"What’s New in the Physiopathology of Acne?" on KindofStephen.