For the past couple of months, I dedicated my columns to report and discuss the results published by Alvarez and coworkers about ingredients recommended by dermatologists.¹ These doctors agree these ingredients efficaciously address one or more of seven skin concerns: fine lines and wrinkles, redness, dark spots, acne, large pores, dry skin and oily skin. 

I stated without hesitation that this publication is a “miracle” insofar as it shows that dermatologists took time to  discuss the activity of cosmetics and therefore acknowledge that cosmetic ingredients can be active. These results reported by Alvarez and coworkers represent a first step. Hopefully they indicate a trend that will contribute to the improvement of our knowledge, and to the consolidation of our belief that active cosmetics are not a pipe dream.

More Than Hope?

How do we move from dreams to reality? First, change our mindset. Moisturization and solar protection, are examples of personal care products that dictate the way of thinking associated to cosmetics. Glycerol is formulated in emulsions and is applied to the surface of the skin, where it maintains water molecules and achieves moisturization. UV filters are applied to the skin and they passively absorb UV radiation on the spot achieving UV protection. We think of these activities (moisturization, sun protection) as of something that happens because of inert foreign molecules that have been slapped on the skin with the hope to achieve a benefit. 

Yet, not all active cosmetics behave this way. Consider the self-tan induced by Diydroxy Acetone (DHA). DHA is applied on the skin and reacts with the free amino acids present in the stratum corneum to form molecules of different colors; mainly brown, gold and orange. These molecules impart to the skin a tan-like color without the need of exposing the skin to damaging UV radiation. 

Let us consider another cosmetic activity: exfoliation. Salicylic acid is a keratolytic agent. It participates in a chemical reaction ending in the breaking of the intercorneocytary bonds to achieves exfoliation, thereby increasing skin smoothness and decreasing the visisbility of surface imperfections. 

So a classical self-tanner and a classical exfoliator do not bring inert foreign molecules to the skin. They bring foreign molecules that react with resident molecules to achieve well-defined biochemical results.

Biochemical Tools

Consider cosmetics as biochemical tools that can dictate a determined behavior of the skin surface. This is the mindset I urge us to acquire. This could open novel ways of thinking that will encourage creativity without sacrificing scientific rigor.

The stratum corneum and the epidermis are rich in enzymes that can be activated or inhibited to achieve well-defined results. Kallicreines and other proteases can be activated by specific molecules and perform exfoliation thus avoiding the stinging of the acids. This attribute is particularly convenient for the exfoliation in the eye zone. 

Arginases synthetize urea, a very good hydrating molecule that is unfortunately tacky when added at high concentrations. The addition of arginase activators provoke the sustainable production of urea on the spot, thus maintining an optimal level of hydration without tackiness. 

Topically applied stable forms of Vitamin C, such as Magnesium Ascorbyl Phosphate, are split by resident enzymes to yield pure Vitamin C. Added Vitamin B3 is biochemically metabolized to NAD+, a molecule necessary to boost post-UV energy production as well as DNA repair, thus reducing UV-induced erythema. 

The production of Hyaluronic Acid in the epidermis can be induced by appropriate inducers. Moisturization can be achieved  in situ without the annoying procedures to deal with the visco-elastic gels that form when Hyaluronic Acid is dissolved in water. 

Aging skin produces excessive small Proline Rich Proteins. They play a role in the onset of pruritus. Inhibitors of their production would be welcome in skincare for the anti-aging category. 

In addition, many cosmetic endpoint could be reached by the proper handling of the microbiome. As a windfall, targeting microorganisms of the microbiome offers a panoply of possibilities for producing helpful molecules in situ or to overcome harmful situations; without violating FDA mandates that strictly forbid cosmetics to physiologically intervene in skin metabolism.

Dermatologists understand the enzymology of the stratum corneum and microbiome characteristics. Derms are the first to applaud an active that is not just a foreign molecule slapped on the skin. Rather, a foreign molecule that will interact with resident molecules to direct them to a specific performance.

Broaden Activity

Secondly, let us broaden the scope of the activity. The paper by Alvarez et al limited the analysis of the cosmetic ingredients to those having an activity in seven domains: fine lines and wrinkles, redness, dark spots, acne, large pores, dry skin and oily skin. With a new mindset, one might be tempted to add other domains. 

What about elasticity and resilience? They can be improved by increasing the pulling effect of keratinocytes toward one another. Radiance, glow and luminosity? They have been observed to recover the characteristics of youth by the application of mildly vaso-dilating vitamins. Body odor? It can be modulated by keeping specific microorganisms under control. Rosacea and eczemas? Controlling the microbiome could be a way to to make rosacea and eczema less severe. Dark circles under the eye? Stretch marks? Constitutive pigmentation? Their domains seem to be “orphans” of treatment endowed with even minimal activity. Somebody could say that they offer a tremendous opportunity for improving our panoply of actives! With a new mindset, there is room for a lot of improvement.

References

1. Alvarez GV et al Skin care ingredients recommended by cosmetic dermatologists: a Delphi consensus study. J. Am. Acad. Dermatol. (2025) In the press.

Paolo Giacomoni, PhD
Insight Analysis Consulting
paologiac@gmail.com
516-769-6904

Paolo Giacomoni acts as an independent consultant to the skin care industry. He served as Executive Director of Research at Estée Lauder and was Head of the Department of Biology with L’Oréal. He has built a record of achievements through research on DNA damage and metabolic impairment induced by UV radiation as well as on the positive effects of vitamins and antioxidants. He has authored more than 100 peer-reviewed publications and has more than 20 patents. He is presently Head of R&D with L.RAPHAEL—The science of beauty—Geneva, Switzerland