The amount and type of melanin pigments, which are polymers produced inside the melanosomes, determine skin color.1,2 While there is tremendous diversity worldwide in the color of human skin, uniform or even skin color (particularly across the face) in an individual is considered a sign of health, attractiveness, and youthfulness and, as such, is aesthetically desirable.3,4 Skin issues involving hyperpigmentation typically arise because of injury and/or advancing age. Exposure to sunlight is the most common cause of hyperpigmentation and is likely a postinflammatory response to ultraviolet (UV) damage to the skin.5,6 Inflammation may lead to hyperpigmentation via several mechanisms, including direct stimulation of melanocytes by inflammatory mediators and reactive oxygen species (ROS) and release of endocrine inducers of pigmentation such as α-melanocytestimulating hormone.6 The resulting melanin production provides protection against future insult, as melanin has both UV absorption and ROS scavenging activities.7
Altered production of cutaneous melanin causes problems of an aesthetic nature. Such disorders of hyperpigmentation, including melasma, postinflammatory hyperpigmentation, solar lentigines, freckles, and dyschromia from photoaging, are very common in humans, and there is a broad interest in newer, more effective treatment modalities. Traditionally, the gold standard topical agent for skin lightening was hydroquinone (HQ) 4%, until regulatory agencies around the world began questioning its safety.8,9 Adverse effects, including skin irritation, contact dermatitis, and exogenous ochronosis may occur with use of this compound. The US Food and Drug Administration has initiated studies to better understand the long-term safety of topical HQ and has not made a determination on its safety10; however, many user interest groups have taken the position that products containing HQ should not be used because of potential safety concerns. As a result, there exists a large and growing market for alternative products that effectively lighten the skin.
While there are an ever-increasing number of cosmetic skinlightening and skin-brightening products in the marketplace, the overwhelming majority lack any clinical studies to support their claims. Most often, manufacturers will utilize in vitro studies (such as tyrosinase inhibition) as a support for efficacy or utilize testimonials from satisfied users.
Employing a unique combination of skin-lightening and proprietary ingredients that address various pathways involved in melanin production and control, 3 formulations were devel-