Tag: acne

Can you mix tretinoin and benzoyl peroxide?

KindofStephen

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!

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

It’s Not Fungal Acne

KindofStephen

Fungal acne is not a diagnosis.

“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.

Adapalene 0.3% may help improve the appearance of atrophic acne scars

KindofStephen

A group of researchers sponsored by Galderma, a subsidiary of Nestle, have published the results of a series of experiments looking at the effect that Adapalene had on the prevention and treatment of atrophic scarring as well as acne.

Source: Art of Dermatology

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

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

KindofStephen 1 Comment

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

What is Differin?

Differin is a topical acne treatment which contains a synthetic retinoid called adapalene. Adapalene is not similar in structure to tretinoin or other retinoic acid compounds. However, like other synthetic retinoids like tazarotene, adapalene activates the same receptor targets in the skin like retinoic acid receptor (RAR) β and γ and retinoid X receptor (RXR).

Adapalene is more stable than tretinoin and can be used in conjunction with benzoyl peroxide. It is also more lipophilic, so more can accumulate within the sebaceous unit.

Differin for Acne

In a head to head comparison, 0.100% adapalene gel  was more effective than a 0.025% tretinoin gel in non-inflammatory (open and closed comedones) and inflammatory (papules and pustules) acne – it was better tolerated as well, which means less irritation.

A multi-ethnic study with Chinese, Malay, Indian, and Caucasian subjects found good tolerability among all races. A separate study on Black South Africans also found efficacy in treating acne and good tolerability.

A meta-analysis of 5 studies that compared 0.100% adapalene gel and 0.025% tretinoin gel also found them similarly effective for acne. Of particular interest, it seems adapalene begins to reduce acne after 1 week of use – which is faster than tretinoin and may be due to adapalene causing less irritation.

Another study showed that 0.1% adapalene gel was less irritating than 0.100%, 0.050%, 0.025% tretinoin and even 0.100% tretinoin microspheres (Retin-A Micro).

A study comparing 0.030% and 0.100% adapalene gel found that the 0.100% adapalene gel was significantly more effective than the 0.030% gel in treating acne.

A supplementary article submitted to Cutis reported a decrease in sebum production on subjects that were using 0.100% adapalene gel for 4 weeks. Sebum production returned to normal after the treatment was stopped. There’s a possible mechanism for adapalene to reduce sebum production by suppressing triglyceride formation in sebocytes – in hamsters.

Differin for Hyperpigmentation

Adapalene seems to also be effective for hyperpigmentation, however there is more research and evidence supporting tretinoin and tazarotene.

A non-blinded study on 65 Black African patients using a 0.100% adapalene gel found significant improvements in hyperpigmentation. Less than 5% of subjects in the study experienced skin irritation.

Studies covered in the next section on Caucasian and Chilean subjects also found brightening in overall skin pigmentation.

Differin for Anti-Ageing

In terms of treating photodamage and photoageing, there is very little research on the topic, especially compared to tretinoin and to a lesser extent tazarotene.

A Galderma study with 0.100% and 0.300% adapalene gel on 90 Caucasian subjects saw improvement in solar lentigines (freckles) and actinic keratoses. Trained dermatologists noticed an improvement in fine skin wrinkling and an overall brightening of the skin’s pigmentation. No significant change in deep wrinkles was noticed. Results were much more pronounced with the 0.3% adapalene gel.

Another Galderma study on Chilean women found similar results. They found marked improvement in skin wrinkling at 90 and 180 days of treatment using a Visia skin analyzer, though they did not differentiate between fine and deep wrinkles. Of interest is that skin thickness did not increase, which is common with tretinoin treatment, however they did find an improvement in abnormal elastin accumulation (elastosis band) in the skin.

Questions and Answers

I’ve gotten a few questions about this on my Instagram, so here they are with their answers!

pricklygoldenpear asks: Can adapalene and other retinoids be used with niacinamide? I mean like layering them. If yes, which one over or under – or are both ways OK?

As with many questions regarding ingredient compatibility and order of application – there’s very little to often no research on the topic. Almost every skin study compare one treatment vs a control treatment. Very rarely do studies look at results from one ingredient, then an additional ingredient, etc. This type of study design is significantly more complex, more time-consuming, and costly to perform.

When looking for studies that examined niacinamide and retinoids, I found none that looked at the combination of niacinamide and tretinoin or adapalene.

A study published in the JCD did compare the use of a retinyl ester (hydroxypinacolone retinoate) with niacinamide, and found an improvement in melasma, however the control cream was just a gel – so we can’t tell which ingredient in particular was responsible for the benefits.

A supplementary article submitted to the JAAD looked at a combination of niacinamide with retinaldehyde and glycolic acid and also found improvements. Again it suffers from the same problem as the previous study – which ingredient was responsible? Were the effects synergistic?

And an open-access paper comparing the combination of niacinamide, two peptides (Pal-KT and Pal-KTTKS), and retinyl propionate found it produced similar effects to 0.02% tretinoin – with less dryness and irritation.

A study published in CCID found that the combination of niacinamide, retinol, and 7-dehydrocholesterol reduced metalloproteinase and other inflammatory markers in the skin.

An in-vivo study on cultured human keratinocytes found that niacinamide could reduce some of the increased expression of aquaporin-3. This increase of aquaporin-3 is thought to increase water permeability – which could lead to skin dryness.

So while none of these studies looked niacinamide and adapalene or tretinoin directly, it seems likely that there should be no issue combining the two.

As to the “proper” ordering of the two topicals, there is no data and I don’t think it really matters. Choose the product with the lowest lipid content first, but above all else: Consistency matters more than product application order.

elspethxieI asks: Is this suitable for mothers who are breastfeeding?

From Medications’ and Mothers’ Milk by Thomas Hale, “Differin Gel (Adapalene 0.1%) is similar to Retin-A (retinoic acid or tretinoin)…Adapalene is virtually unabsorbed when applied topically to the skin. Plasma levels are almost undetectable, so milk levels would be infinitesimally low and probably undetectable.”

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

KindofStephen

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

A naturally-occurring system discovered in bacteria holds promise as a way to fight pathogens – very specifically and without the risk of antibiotic resistance.

Only problem is right now the process involves using an electric shock, but scientists are working on a not so-painful method!

In vivo study of comedone reformation

KindofStephen

Using a microscopy technique researchers were able to “watch” what happened to a comedone a week after it was removed.

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.