Superior even skin tone and anti‐ageing benefit of a combination of 4‐hexylresorcinol and niacinamide

OBJECTIVES: To demonstrate the synergistic effect of 4‐hexylresorcinol (4‐HR) with niacinamide in boosting anti‐melanogenic efficacy in vitro and establish the in vivo efficacy and safety of the combination in a human trial. METHODS: Primary human epidermal melanocytes and 3D pigmented skin equivalents were treated with 4‐HR, niacinamide, and their combinations for their effect on pigmentation. This was followed by a randomized, double‐blind, split‐face clinical study in Chinese subjects, and effects on skin tone, hyperpigmentation, fine lines and wrinkles, hydration, and skin firmness were measured for a 12‐week study period. RESULTS: In vitro tyrosinase enzyme activity studies showed that 4‐HR is one of the most potent tyrosinase inhibitors. The combination of 4‐HR and niacinamide showed a synergistic reduction in melanin production in cultured melanocytes and lightened the 3D skin equivalent model. In vitro as well as in the human trial, the combination of 4‐HR and niacinamide showed significantly improved efficacy over niacinamide alone on hyperpigmentation spots as measured by L*, the visual appearance of fine lines and wrinkles in crow's feet and perioral area and skin firmness, with no product‐related adverse events. CONCLUSIONS: A formulation containing a combination of 4‐HR and niacinamide delivered superior skin tone and anti‐ageing benefits significantly better than niacinamide alone with no adverse events. This study demonstrates that a product designed to affect multiple pathways of melanogenesis, inflammation, and ageing may provide an additional treatment option, beyond hydroquinone and retinoids, for hyperpigmentation and ageing.