Tolerance and Efficacy of a Product Containing Ellagic and Salicylic Acids in Reducing Hyperpigmentation and Dark Spots in Comparison With 4% Hydroquinone

January 2013 | Volume 12 | Issue 1 | Original Article | 52 | Copyright © January 2013


Amanda Dahl BS, Margarita Yatskayer MS, Susana Raab BS, and Christian Oresajo PhD

L’Oréal USA, Clark, NJ

Abstract
Hydroquinone (HQ) is the benchmark prescription agent for skin lightening. However, HQ use is recently banned in Europe and in parts of Asia because of potential long-term consequences, including carcinogenesis when orally consumed. This has resulted in development of alternative skin-lightening agents with comparable efficacy to HQ, but better safety profiles. This study examined the skin-lightening ability of a topical product containing 0.5% ellagic acid and 0.1% salicylic acid and compared its efficacy with that of a prescription generic 4% HQ product. Fifty-four multiethnic subjects were randomly assigned to use the topical test formulation or generic 4% HQ twice daily for 12 weeks to evaluate product tolerability and efficacy. Under the conditions of this double-blinded clinical study, the test product demonstrated comparable tolerance and efficacy to that of a benchmark product 4% HQ, as assessed by clinical grading, physical measurement of spot size using image analysis, and questionnaire response analysis. This study suggests that this new product provided comparable skin depigmentation benefit to the benchmark product. In addition, the product appears to have better esthetics (texture, pleasantness to use, skin feel) than the 4% HQ product.

J Drugs Dermatol. 2013;12(1):52-58.

INTRODUCTION

For decades, the standard prescription treatment for facial skin lightening is topical hydroquinone (HQ).1 Recently, its safety has been questioned. Hydroquinone is currently banned in Europe and parts of Asia because of concerns about oral toxicity and carcinogenicity.2,3 A phenolic compound, HQ functions by inhibiting the enzymatic oxidation of tyrosine and phenol oxides. Among other activities, it covalently binds to histidine or interacts with copper at the active site of the rate-limiting enzyme tyrosinase. Because of these activities, HQ suppresses the melanocyte metabolic processes, resulting in decreased melanin pigment production.4
While HQ is still the most efficacious substance for lightening skin, research aimed at developing other skin-lightening ingredients with comparable efficacy to HQ has progressed. One approach to enhancing the skin-lightening effect of various ingredients is to combine them in formulations to maximize efficacy.
A variety of plant extracts or plant-derived ingredients such as ellagic acid have been used as effective skin lighteners.5,6 Ellagic acid has been demonstrated to have melanogenic inhibitory activity both in vitro and in vivo.7-9 Many plant extracts have activities that make them ideal for skin-lightening activities, including metal-chelating activity, antioxidant activity, or anti-inflammatory activities.6 All these activities can help reduce melanin synthesis by inhibiting tyrosinase activity by binding to copper, or by blocking the polymerization of melanin.10 In order to increase the skin-lightening activity of a specific plant extract, it may be combined with other extracts with a different activity or the formulation may be optimized to include stabilizers, penetration enhancers, or a keratolytic agent such as salicylic acid.11
Although there are a variety of skin-lightening and spot-reducing products on the market, most of these products do not show efficacies similar to that of the gold standard, 4% HQ. A successful skin-lightening alternative to HQ should remove existing pigment from the skin, decrease melanin synthesis, and prevent melanin transfer to the melanocytes. In this study, we compared 4% HQ with a topical product containing ellagic acid and other plant extracts in combination with salicylic acid in a stabilized formulation in a multiethnic panel or patients with hyperpigmentation and dark spots on the face.

MATERIALS AND METHODS

Subjects

This was a randomized evaluation comparing the efficacy and tolerance of 2 facial treatment products. A total of 54 multiethnic female subjects aged 30 to 65 years with Fitzpatrick skin types I to VI who demonstrated mild to moderate dark spots/sun spots/hyperpigmentation, uneven skin tone, and loss of firmness/elasticity were recruited. The number of individuals from each ethnic group—Caucasian, African American, Hispanic, and Asian—was balanced approximately equally for treatment with each of the 2 test products. All subjects were given an identical supporting facial product, SPF 15 moisturizer for use in the morning, and moisturizer to use as needed in the evening for the duration of the 12-week test period. Subjects were randomized and given test products for twice-daily application to their entire face.
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