INTRODUCTION
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-
