In the past couple of months, all the journals interested in the skincare industry have quoted and applauded the paper by Alvarez and coworkers.¹ It reported on the ingredients recommended by dermatologist to address one or more of seven skin concerns: fine lines and wrinkles, redness, dark spots, acne, large pores, dry skin, and oily skin. 

Upon reading the paper, I did not hesitate in claiming that this publication was a “miracle” insofar as, as I wrote in September, “dermatologists across the country have decided to discuss the activity of cosmetics. Once thought of as an oxymoron…cosmetic activity does exist and the interest shown by those dermatologists will encourage scientists committed to cosmetic science, to persevere in their endeavor”. I also wrote that “the results reported by Alvarez and coworkers are just a beginning. They are not complete and they provide results consistent with a medical-dermatological mindset.”

Post-Miracle

Perhaps the most important thing to do, after a “miracle” has been recognized, is to understand the methodology of the work performed and to find its boundaries. An undefined group of scientists performed a literature search on papers published between 1990 and 2020. Their goal was to identify ingredients intended for the treatment of those seven skin concerns. A long list of ingredients (318) was made that was reviewed by an expert panel of 17 cosmetic dermatologists. 

As written in the Methods section of the paper by Alvarez and coworkers, these dermatologists were asked “to identify the ingredients that they believed were most useful”. But in the Introduction of that same paper it is written that “the study was aimed at determining which generic topical ingredients are most frequently recommended by experts in cosmetic dermatology for common dermatologic skin concerns.”  

This ambiguity ( most useful versus most frequently recommended) must not be overlooked if we try and understand some unexpected results in the paper by Alvarez and coworkers. 

The 17 dermatologists reduced this list to 83 and a group of 62 dermatologists reviewed this list and, if necessary, suggested other ingredients. Ultimately they ended up with a list of 23 ingredients. It included one additional ingredient (ceramide) that was not present in the first list of 83. 

This list of 23 was detailed in this column last month. As I pointed out, the 23 ingredients that were consensually recognized as useful (or active or frequently recommended), are not surprising; they are all well known to good cosmetic chemists and marketing executives in the skincare industry. What one could find surprising is that some active ingredients have not been recognized (or reported) as such in the paper by Alvarez and coworkers, in spite of published evidence.

More Work Needed

To make it so that the “miracle” becomes fruitful, what is needed is to point out those active ingredients that might have escaped the attention of dermatologists. This means that there is much work left to do, to bring to light the existence of other active ingredients and enlarge the panoply of the raw materials that can be used with the reasonable expectation of formulating active concoctions. It may even require branching out into areas other than the seven skin concerns considered by the paper by Alvarez and coworkers.

I will try and provide some references relative to the cosmetically interesting activity of some natural ingredients.

Anti-Inflammatories 

Several anti-inflammatory agents are used in cosmetic products. One could surmise that the dermatologists establishing the list of 318 did not consider anti-inflammatory agents since the word “anti-inflammatory” is a word banished from the cosmetic world. Yet, pseudopterosins from the Sea Whip are excellent anti-inflammatory agents^2,3,4

In the late 1990 and early 2000 a Sea Whip extract was successfully used in a product incredibly active for instance, against post-UV erythema. I note it because that formula is no longer on the market. It was called Exceptionally Sooting Lotion for Upset Skin and was marketed by Clinique. Paradoxically, today’s Clinique analog product is called Exceptionally Soothing Cream for Upset Skin Anti-Itch. It does not contain the Sea Whip extract but it does contain hydrocortisone acetate… an ingredient that did not reach consensus among the dermatologists and does not appear in the list of the 23 most useful or most frequently recommended ingredients.

Another natural anti-inflammatory agent is Melatonin. Several clinical studies were performed analyzing the effect of topically applied melatonin on human skin before exposure to radiation such as UV, sunlight and high-energy beams.⁵ They were all characterized by an appropriate design (randomized, double-blind, and placebo-controlled). The study results strongly support the clinical efficacy of melatonin in preventing or reducing skin damage such as dermatitis, erythema and sunburn.

The Power of Vitamins

Another natural product that has not been considered in the paper by Alvarez and coworkers is vitamin E. Yet, vitamin E in nanocapsules was formulated in Lancôme’s Primordial in the late 1990s and was successfully tested in clinical trials. The presence of vitamin E on human skin exposed to UV radiation protects the skin against bleb formation in keratinocytes and maintains the morphology of the epidermis that is otherwise remarkably affected by solar radiation.^6,7

A very effective agent against itch is Zanthalene, the tradename for an extract of Zanthoxylum bungeanum. To my knowledge, the only published material consists of reviews of the plant’s therapeutical activities in the frame of Traditional Chinese Medicine without presenting controlled clinical data. I urge the suppliers of Zanthalene to spend the necessary time and publish solid clinical data on its anti-itch effects, and possibly other effects.

As far as other active ingredients are concerned, we know that Bakuchiol outperforms Retinol.^8,9 It should be taken into consideration as an active ingredient, since retinoids have been consensually considered useful as reported by Alvarez and coworkers. We also know that Acetyl Zingerone is of extreme utility in sunscreens because of its capability of neutralizing singlet Oxygen, the most harmful of the UV-induced Reactive Oxygen Species.¹⁰

I encourage the distributors of interesting raw materials to provide the dermatological community with solid, controlled clinical data and with pertinent publications demonstrating the activity and the usefulness of their raw materials in skincare.

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.
2. Look SA et al (1986) The pseudopterosins: Anti-inflammatory and analgesic natural products from the sea whip Pseudopterogorgia elisabethae. Proc Natl Acad Sci 83 : 6238-6240
3. Correa H et al Anti-inflammatory effects of the gorgonian Pseudopterogorgia elisabethae collected at the Islands of Providencia and San Andres (SW Caribbean). J. Inflamm. 6 , 5 (2009)  https://doi.org/10.1186/1476-9255-6-5
4. Ata A Identification of anti-inflammatory diterpenes from the marine gorgonian Pseudopterogorgia elisabethae Tetrahedron (2003) 59 : 4215-4222
5. Greco G et al Clinical Studies using topical melatonin.  Int J Mol Sci. 2024 May 9;25(10):5167. doi: 10.3390/ijms25105167
6. Giacomoni, PU et al UV-induced ultrastructural modifications of keratinocytes in human epidermis: protection by vitamin E. J. Invest. Dermatol. (1996) 107 657
7. Giacomoni PU et al Morphological alterations and cell blebbing in UV-irradiated human epidermis. Arch. Dermatol. Res. (1998)  290 : 163-166
8. Dhaliwal et al (2019) Prospective, randomized, double-blind assessment of topical bakuchiol and retinol for facial photoaging. British Journal of Dermatology 180, pp289–296
9. Bluemke et al (2022) Multidirectional activity of Bakuchiol against cellular mechanisms of facial ageing – Experimental evidence for a holistic treatment approach. Int J Cosmet Sci 44 : 377-393
10. Meyer TA, et al Acetyl Zingerone: A Photostable Multifunctional Skincare Ingredient That Combats Features of Intrinsic and Extrinsic Skin Aging. Antioxidants (Basel). 2023 12 :1168.

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 .