Octadecenedioic Acid: an alternative to azelaic acid, adds skin lightening

Octadecenedioic acid: A new ingredient with pleotropic benefits for skin

Anthony Rawlings, PhD, AVR Consulting Ltd, Northwich, United Kingdom; Johann Wiechers, PhD, Uniqema, Gouda, Netherlands; Jean-Claude Nicolas, PhD, INSERM, Montpellier, France; Marie-Dominique Galbert, PhD, University of Rennes, Rennes, France

Azelaic acid, a dicarboxylic acid, is known to reduce the symptoms of acne and rosacea as well as reducing skin melanogenesis. In the search for a higher efficacy compound, octadecenedioic acid was developed. Examining its structure, it was proposed that octadecenedioic acid may act similarly to azelaic acid as an antimicrobial agent. However, due to the increased carbon chain length of the compound it is also anticipated to bind to the peroxisome proliferator-activated receptor (PPAR), unlike azelaic acid. As a result on binding to PPAR, octadecenedioic acid will possess multiple activities (eg, promoting keratinocyte differentiation as well as possessing antimicrobial properties). Binding to chimeric PPARs in vitro in cell-based reporter assays demonstrated that although octadecenedioic acid is a pan- PPAR agonist, it posses slightly more affinity for the PPAR-g isoform. Additionally, microbial in vitro studies demonstrated that octadecenedioic acid was 50-fold more active than azelaic acid at inhibiting the growth of Propionibacterium acnes. In vitro skin delivery studies also demonstrated a preference for transfollicular delivery for the octadecenedioic acid compared with azelaic acid. In clinical trials comparing octadecenedioic acid (2%) with azelaic acid (20%) and benzoyl peroxide (5%), octadecenedioic acid compared favorably but without the somatosensory negative effects. We believe it is an effect induced by binding to PPAR-g as well as its antimicrobial activity. Moreover, as it has also been proven to inhibit melanogenesis in vitro, it could also help reduce hyperpigmentation reactions in skin of color. In clinical studies involving 20 subjects, the skin-lightening activity of a 2% octadecenedioic acid–containing formulation was compared with that of a placebo. A significant reduction (P <.025) in skin color could be demonstrated after 8 weeks. This latter effect appears to be related to reduced tyrosinase message and protein levels leading to reduced melanogenesis, which we believe is an effect induced by binding to PPAR-g. In conclusion, octadecenedioic acid appears to be an effective antiacne agent delivering benefits similar to those of azelaic acid but at much lower concentrations; it reduces skin pigmentation and we anticipate on a mechanistic basis that it may also be beneficial for the treatment of rosacea.

Author disclosure: Dr Wiechers is a consultant for Uniqema. 100% sponsored by Uniqema.

Poster Discussion Session P120, American Academy of Dermatology, 64th Annual Meeting, March 3-7 2006, San Francisco.

Supplement to Journal of The American Academy of Dermatology, March 2006, Volume 54, Number 3.

• JAAD Poster Abstracts Online

Appears to be related to some other recent publications

A new mechanism of action for skin whitening agents: binding to the peroxisome proliferator-activated receptor, J. W. Wiechers, A. V. Rawlings, C. Garcia, C. Chesné, P. Balaguer, J. C. Nicolas, S. Corre and M.-D. Galibert, International Journal of Cosmetic Science, Volume 27 Page 123 - April 2005

Octadecenedioic acid is known as a skin whitening agent but its activity is not mediated via a direct inhibition of tyrosinase. Based on the secondary properties of this molecule, such as its anti-inflammatory and anti-ageing effects, we postulated that octadecenedioic acid interacted with the peroxisome proliferator-activated receptor (PPAR) as this nuclear receptor also mediates these effects.

Read more about: finacea