Category: Blog

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

Comparison of skin hydration in combination and single use of common moisturizers (cream, toner, and spray water)

KindofStephen

What’s the best way to organize your skincare routine? Should we layer from thickest to thinnest? Where does sunscreen go?

I’ve been asked this a lot and I don’t have the answer. Most research on skincare application is done with just one product. Sunscreens are always tested on clean skin with no other products. If you want to get as close to the protection on the label, it’s best to recreate the conditions it was tested on, which means applying it on clean skin and not following it with anything else. The same applies for most cosmetic products as well.

That’s not realistic for everyone and many of us enjoy using multiple products. But the reality with a lot of the advice found online and from experts is that it’s just advice and often isn’t based on evidence – especially scientific evidence.

A group of Chinese researchers performed an experiment looking at the effect of different combinations of three products (moisturizer, toner, and mineral water sprays) and different application routines on skin moisture. Keep in mind that the only endpoint measured was stratum corneum moisture measured by the Corneometer, a capacitance measuring tool often used in cosmetic research. This experiment doesn’t provide any insight beyond skin moisture, like skin penetration of an active affected by combination or routine, for example.

20 female volunteers participated in this experiment. Eight 3-by-3 cm squares were drawn on the legs and forearms of each volunteer and were randomized to receive eight different routines and combinations – including a square with no product applied, acting as a control. The baseline moisture levels of the squares were measured and categorized into ‘normal’ or ‘dry’ by a limit of 35 a.u. (a measurement unit used by the Corneometer).

The 8 different combinations and routines are as follows;

Toner and Toner reapplied every 2 hours (T-T)
Cream then Toner together (C+T)
Toner only (T)
Cream only (C)
Cream then Water reapplied every 2 hours (C-S)
Untreated (Control)
Cream and Toner reapplied every 2 hours (C-T)
Toner then Cream together (T+C)

Stratum corneum moisture levels were measured every 2 hours, including a baseline, and participants were kept in a 22 °C room with a 50% humidity.

The products included in the test were a Winona brand Cream with the ingredients:

Aqua, Glycerol, Butyrospermum Parkii Oil, Dimethicone, Glycereth-26, Tridecyl Trimellitate, Pentylene Glycol, Hexyldecanol, Sucrose Polystearate, Diethylhexyl Cyclohexane, Petroleum Jelly, Tocopheryl Acetate, Prinsepia Utilis Royle Oil, Portulaca Oleracea Extract, Beta Glucans, Sodium Hyaluronate, Cetylhydroxyproline Palmitamide, Alpha Bisabolol, Cetearyl Alcohol, Hydrogenated Polyisobutene, Acrylamide, Acrylamide/ammonium Acrylate Copolymer, Acrylates/c10-30 Alkyl Acrylate Crosspolymer, Tween 20, Xanthan Gum, Disodium Edta, Polybutene, Polyisobutene, Butyl Stearate, Stearic Acid, Phenoxyethanol, Ethylhexylglycerin

a Winona brand Toner with the ingredients:

Aqua, Pentylene Glycol, Glycerol, Glycereth-26, Trimethylpentanediol/adipic Acid/glycerin Crosspolymer,
Portulaca Oleracea Extract, Beta Glucan, Sodium Hyaluronate, Hydroxyethyl Cellulose

and Avene Thermal Spring Water was used as the Mineral Water Spray.

While applying any form of skincare product created an increase in skin moisture in dry and normal skin, some combinations were significantly more effective than others.

Table VI is mislabeled and is the data for Dry Skin

Because the normal or dry categories were determined by Corneometer, there’s no way to self-categorize unless you have a Corneometer handy.

From this experiment, the increase in moisture from Cream then Toner, or Toner then Cream, or Cream only were about the same. This implies that the total amount of cream and toner applied is more important than the order of application. As well, this also implies that the increase in moisture is mostly from the cream and not the toner.

The researchers speculate that the increase in moisture reaches a peak depending on factors like the environment which slowly declines after application. Toner on its own did increase moisture of the skin, but even when combined with cream never surpassed the moisture gained from cream alone.

In terms of supplementation of Cream with Water or Toner, the greatest increase in moisture was achieved with application of a Cream then Toner every 2 hours. Supplementation of Water after Cream application reduced skin moisture with each application. Toner with additional Toner supplementation increased skin moisture over time, but was still less than Cream and Toner.

I think reading descriptions of the effects is likely a bit confusing, so I encourage you to use the interactive charts to compare different applications.

Also keep in mind that this experiment used three specific products and concentration of ingredients will vary between products. So it’s best to use this information as a guideline, but not a rule.

Li Yuanxi, Wei Hua, Lidan Xiong, Li Li, Comparison of Skin Hydration in Combination and Single Use of Common Moisturizers (Cream, Toner, and Spray Water), Journal of Cosmetic Science (2016), PMID: 29394018

US FDA warns that biotin supplements can interfere with lab tests

KindofStephen

Are you taking biotin for your skin and nails? Be aware that biotin supplements can interfere with many lab tests. Some of the currently known interactions are tests measuring amounts of troponin, which are often used to diagnose heart attacks. Biotin supplements may also interfere with tests measuring hormone levels involving the thyroid.

The FDA is warning and helping to raise awareness of this side-effect,

“Biotin in blood or other samples taken from patients who are ingesting high levels of biotin in dietary supplements can cause clinically significant incorrect lab test results. The FDA has seen an increase in the number of reported adverse events, including one death, related to biotin interference with lab tests.”

Their recommendation for consumers is to talk to their healthcare provider about biotin supplements and for healthcare professionals to report adverse events to the FDA through the MedWatch report system.

I know supplements seem like an effective way to boost your beauty, because who doesn’t like the concept of beauty from within? But be aware that supplement claims are not regulated by the US FDA, nor do they require testing or approval.

“Federal law does not require dietary supplements to be proven safe to FDA’s satisfaction before they are marketed”

“For most claims made in the labeling of dietary supplements, the law does not require the manufacturer or seller to prove to FDA’s satisfaction that the claim is accurate or truthful before it appears on the product”

The US supplement industry is huge, poorly regulated, generally poorly backed by research, and has large profit margins. It’s easy to see why it can be an attractive market to enter, but don’t trust your health to anecdotal evidence.

Visualizing how a daily sunscreen can protect the skin from UV damage

KindofStephen

Optical coherence tomography and reflectance confocal microscopy can be used to non-invasively to visualize deep into the skin. Using these techniques we can actually see changes in the structure of the skin and its cells.

This group of researchers with funding from La Roche Posay used the imaging techniques to compare the effect of UVB exposure on skin protected with a high SPF and UVAPF sunscreen and skin that wasn’t protected.

What they found was that doses of UVB that caused long-lasting erythema (redness) caused morphological changes in the skin. Changes observed were spongiosis (abnormal accumulation of fluid), microvesicles, sunburn cells, and blood vessel dilation. None of these were observed in skin that was protected by the sunscreen.

A minimal erythemal dose or MED is the amount of UV energy that causes long-lasting redness in the skin. Just 1 MED was enough to cause morphological changes and 2 caused significantly more. This also relates to SPF. An SPF of 2 would provide enough protection to protect an average population against 2 MEDs.

If reducing your risk of developing skin cancers and preventing photoaging are a goal of yours – this is a great reminder and justification to wear your sunscreen daily!

Antonio Gomes-Neto, Paula Aguilera, Leonor Prieto, Sophie Seité, Dominique Moyal, Cristina Carrera, Josep Malvehy, Susana Puig, Efficacy of a Daily Protective Moisturizer with High UVB and UVA Photoprotection in Decreasing Ultraviolet Damage: Evaluation by Reflectance Confocal Microscopy, Acta Dermato-Venereologica (2018), DOI: 10.2340/00015555-2736

What’s causing sunscreen to stain clothing?

KindofStephen

Yellow stains on your clothing? Your sunscreen might be a culprit!

A group of researchers tested 32 commercial sunscreens for their ability to stain white and black 100% cotton.

Of the tested sunscreens; Alba Botanica Hawaiian SPF 50 Spray, L’Oreal Invisible Protect SPF 50, Solbar Thirty, and Aveeno Protect and Hydrate SPF 50 were among the most staining sunscreens.

The least staining sunscreens were; Cerave Baby, Solbar Zinc 38, Cerave Face SPF50, and Babyganics Mineral Based SPF 50

Using statistical analysis to group the sunscreens by sunscreen ingredients they created four distinct groups. Based on these groupings they tested 8 sunscreen ingredients; Avobenzone, Homosalate, Octinoxate, Octisalate, Octocrylene, Oxybenzone, Titanium Dioxide, and Zinc Oxide.

For white fabric; Avobenzone was a strong yellow stainer and so was Oxybenzone to a lesser extent. Titanium Dioxide and Zinc Oxide both left faint white stains.

For dark blue fabric; Avobenzone and Oxybenzone both left faint white staining, but Titanium Dioxide and Zinc Oxide left strong white stains.

The sunscreen ingredients were applied directly to the fabric, whereas in real-life it’s likely transferred to skin by friction and smearing throughout the day

A sunscreen that stains is by no means a reflection of its ability to protect your skin from UV. If reducing extrinsic photoaging is a goal, it’s important to use a sunscreen frequently. Often people are discouraged from using sunscreens because of the texture, scent, and in some cases staining of their clothes.

If staining is an issue I’ve had good luck with soaking it with 99% isopropyl alcohol and then a soak in sodium percarbonate (Oxiclean) or hydrogen peroxide.

Cornell also has a great stain guide for a myriad of stains.

Ginnetti M, Buhnerkempe M, Wilson M, The staining of clothing by
sunscreens: a pilot study, Journal of the American Academy of Dermatology (2018), doi: 10.1016/j.jaad.2018.02.022

Mushrooms aren’t people! Or why human clinical studies are the gold standard

KindofStephen

Marketing language of skincare often leaves out on “what” the tests were done. Leading the consumer to believe that the testing was done on someone like them.

For many products aimed at treating hyperpigmentation, the claims are often based on the inhibition of tyrosinase, an enzyme found in plants and animals that plays a role in the creation of melanin. So it makes sense why inhibiting the effect of tyrosinase would lead to a decrease in melanin production in the skin. What’s often left out, is that most of these tests are performed on tyrosinase derived from the Agaricus bisporus mushroom.

What’s important to understand is that though the enzyme group may be the same, the structure and environment isn’t. Mushroom tyrosinase and human tyrosinase (hTyr) have different catalytic activities and substrate affinities.

Mushroom tyrosinase is easily accessed, commercially available, and cheap. Human tyrosinase until recently was difficult to produce and isolate.

As early as 2013, a group of researchers led by Petra Cordes were able to express hTyr in human kidney cells and then isolate them. This allowed them to 3D map the enzyme and use them in further tests.

Building upon this, scientists from Beiersdorf screened 50,000 compounds to see which ones effectively inhibited hTyr. What they found was interesting, but not surprising.

Some compounds which are very effective in inhibiting mushroom tyrosinase (like hydroquinone, arbutin, and kojic acid) had a reduced or minimal effect on hTyr.

Of the 50,000 compounds tested, thiazolyl-resorcinols were the most promising. They then modified it to be compatible with topical formulations leading to isobutylamido thiazolyl resorcinol.

An interesting thing they found about hydroquinone and its precursors like arbutin was their activity may be due to a cytotoxic effect on melanocytes. Their experiment showed a long-term reduction in melanocyte activity even after the hydroquinone or arbutin was stopped.

The group at Beiersdorf then went on to test 0.2% isobutylamido thiazolyl resorcinol on a group of humans for 4 weeks and were able to see a statistically significant and clinically relevant decrease in hyperpigmentation.

It’s very likely that Beiersdorf will patent the use of isbutlamido thiazolyl resorcinol for treating hyperpigmentation, especially if further human clinical trials are positive, but their methods for performing this test on human tyrosinase in MelanoDerm skin models have been shared with the scientific community.

Mann T, Gerwat W, Batzer J, Eggers K, Scherner C, Wenck H, Stäb F, Hearing VJ, Röhm K-H, Kolbe L, Inhibition of Human Tyrosinase Requires Molecular Motifs Distinctively Different from Mushroom Tyrosinase, The Journal of Investigative Dermatology (2018), doi: 10.1016/j.jid.2018.01.019.