INTRODUCTION
Increasing demand among consumers for naturally derived or botanical ingredients in skin care products has led to the development of numerous over-the-counter or physician-dispensed cosmeceutical products that are marketed as having natural active ingredients. Among patients and consumers with darker skin types, interest in newer products that promote an even skin tone and/or improve hyperpigmentation is especially strong. Over the past 15 years, a growing list of products containing naturally derived or botanical active ingredients with effects on hyperpigmentation have been evaluated in blinded, controlled clinical studies (Table 1). Knowledge of these products is useful to the practicing dermatologist so that questions from patients about non-prescription options can be answered effectively and the potential to use such products as adjunctive, maintenance, or alternative therapy in the management of dyschromias can be considered. In this article, naturally derived active ingredients with effects on hyperpigmentation are reviewed, with a focus on those that have been evaluated in published clinical trials.
Soy
Soy contains a variety of active components, including phytosterols, which help restore barrier function and replenish moisture; vitamin E, an antioxidant; large soy proteins, which provide skin smoothing and softening effects; and natural soy surfactants, which provide a gentle cleansing action. Soybeans contain small protein serine protease inhibitors, Bowman-Birk inhibitor, and soybean trypsin inhibitor, all of which have been shown to inhibit the proteinase-activated receptor-2 (PAR-2) pathway.2 PAR-2 is a G-protein couple receptor that regulates phagocytosis of melanosomes by keratinocytes. Inhibition of this pathway reduces this phagocytosis, leading to reduced melanin transfer and reduced cutaneous pigmentation.3 Small soybean-derived proteins have been shown to reduce ultraviolet B (UVB)-induced pigmentation.2
In a study of 16 Latina women with mottled pigmentation, a stabilized total soy extract was applied once daily to the areas of dyspigmentation for 3 months, with untreated areas of dyspigmented lesions serving as controls. Improvements were observed in 14 of the 16 subjects, with a mean reduction in hyperpigmentation of 12%.4 A larger double-blind, placebo-controlled, 12-week clinical study was conducted comparing a soy-containing moisturizer with broad spectrum sunscreen (SPF 30) with its vehicle (also containing sunscreen). Enrolled in the study were 68 participants between 30 and 50 years old, with moderate levels of skin roughness, blotchiness, and mottled hyperpigmentation, who applied product daily. Significant improvements in the mean scores for fine lines, mottled hyperpigmentation, blotchiness, and skin clarity were observed as early as week 2 when compared with baseline values. At week 12, patients using the soy-containing moisturizer with
