In Vitro and In Vivo Efficacy and Tolerability of a Non-Hydroquinone, Multi-Action Skin Tone Correcting Cream

July 2019 | Volume 18 | Issue 7 | Original Article | 642 | Copyright © July 2019

Pearl E. Grimes MD,a David H. McDaniel MD,b Mitchell Wortzman PhD,c Diane Nelson RN MPHc


aVitiligo & Pigmentation Institute of Southern California, Los Angeles, CA

bMcDaniel Institute of Anti-Aging Research, Virginia Beach, VA

cskinbetter science LLC, Phoenix, AZ 


Background: Pigmentation disorders are therapeutically challenging to treat, requiring complicated regimens. 

Alternatives to hydroquinone (HQ) are desired. We evaluated the efficacy and tolerability of a non-HQ multi-action skin tone corrector (ETCS) developed to inhibit melanin production and improve skin quality. 

Design and Methods:
Twice-daily use of ETCS and ETCS + AHA-Ret, a retinoid-based alpha hydroxy acid cream, was evaluated in subjects with mild to severe dyschromia. Digital images were obtained at baseline, 4, 8, and 12 weeks and included assessment of dyschromia, erythema, fine lines/wrinkles, pores, texture, and global improvement. Melanin Index (MI) measurements were obtained at baseline, 4, 8, and 12 weeks. Subject self-assessments were obtained over the course of the study. Adverse Events (AEs) were collected throughout the study. An extension study evaluated use over 16-weeks. 

Significant mean reductions from baseline occurred in dyschromia for ETCS (n=42) and ETCS + AHA-Ret (n=10) over 12 weeks (P<0.0001, each). Significant mean reductions from baseline in MI were achieved in both groups at every timepoint (ETCS: P<0.0001; ETCS + AHA-Ret: P<0.02, 4 weeks; P<0.0001, 8 and 12 weeks). Substantial improvements were demonstrated in global improvement, fine lines/wrinkles, erythema, pores, and texture at 12 weeks. Reductions from baseline occurred in dyschromia and MI (P<0.0001, each) at 16 weeks. High levels of subject satisfaction were reported with nearly all subjects reporting reduced appearance of uneven skin tone/discoloration and lightened darker patches, and improvement in overall skin tone. Mild, transient AEs were reported with no discontinuations due to an AE.

Twice daily use of ETCS led to early, significant reductions in dyschromia and melanin index. Combination use with a retinoid-based, AHA cream in the evening demonstrated enhanced reductions. ETCS effectively reduced hyperpigmentation, improved overall skin appearance, and was highly tolerable.

J Drugs Dermatol. 2019;18(7):642-648. 


Dyschromia caused by photodamage is a common cosmetic concern, with more than 5.5 million patients having a sole diagnosis of dyschromia or hyperpigmentation.1 Often a chief complaint reported to dermatologists by women with skin of color,2 facial hyperpigmentation can have a substantial negative psychosocial impact on self-esteem and quality of life1-3 and is challenging to treat.

The initiation and extent of pigmentation may be influenced by intrinsic (age, ethnicity, hormonal changes) and extrinsic (stress, inflammation, UV exposure) factors.4 Epidermal melanin content is significantly greater (up to 2-fold) in chronically, photo-exposed vs. photo-protected skin, regardless of skin color.5 Disruption or deregulation of production of melanin leads to skin pigmentary disorders.6,7 A greater understanding of the pathophysiology of pigmentation has led to the development of treatments targeting the underlying pathways involved in melanogenesis.

Melanogenesis or melanin production is based on a complex biochemical process that involves multiple pathways.8 The core cell signaling pathways that affect skin pigmentation include melanocyte activation, melanosome formation, melanin synthesis, melanin transfer, and melanin removal.8 Melanocyte activation can be triggered by UV exposure, inflammation, pregnancy, and aging. Melanin production results from tyrosinase-mediated synthesis of melanin. Tyrosinase is a key enzymatic regulator of melanin production.9 L-Tyrosine, in the presence of tyrosinase, is converted to dopaquinone (DOPA) and then to either eumelanin (black-brown melanin) or pheomelanin (yellow-red melanin).

Disorders of hyperpigmentation include melasma, dyschromia, post-inflammatory hyperpigmentation (PIH), and solar lentigines.7,10,11 Hyperpigmentation manifests as patches of uneven skin color and is most frequently caused by UV exposure. Successful treatment of hyperpigmentation often requires multiple