Novel Cyclized Hexapeptide-9 Outperforms Retinol Against Skin Aging: A Randomized, Double-Blinded, Active- and...

The functionality and regenerative capacity of skin progressively deteriorate with aging. Topical use of peptides with a hyper-safety profile has been implicated in replacing retinol for skin anti-aging use, but is limited due to low stability and poor skin permeability.

In this randomized, double-blinded, active- and vehicle-controlled clinical trial, we aim to evaluate the efficacy of an innovative cyclized hexapeptide-9 (CHP-9) with increased stability and skin permeability on skin aging compared to retinol.

Healthy volunteers with aging skin were randomly assigned to twice-daily topical use of 0.002% CHP-9 serum, 0.002% retinol serum, or vehicle serum for 56 days.

CHP-9 treatment significantly decreased the number, area, and roughness of both crow's feet (-2.20, 95% CI: -4.38, -0.03; -3.95, 95% CI: -5.80, -2.11; -1.95, 95% CI: -3.30, -0.59, respectively) and forehead wrinkles (-2.88, 95% CI: -4.21, -1.56; -4.90, 95% CI: -5.97, -3.82; -3.96, 95% CI: -5.92, -2.01, respectively), while retinol only decreased the area of crow's feet (-2.23, 95% CI: -3.86, -0.60) and the number and area of forehead wrinkles (-1.05, 95% CI:-1.69, -0.41). Except for the roughness of crow's feet, CHP-9 demonstrated significantly larger extent of effects than retinol did on all other outcomes. Furthermore, long-term use of CHP-9 showed time-dependent augmentation in its potency to reduce the number of crow's feet, and the number, area, and roughness of forehead wrinkles.

In conclusion, CHP-9 is more potent than retinol in improving skin aging-related symptoms, especially for long-term use. Cyclization of collagen peptides may present a preventive/therapeutic option for skin aging.