Impact of Ceramide Acyl Chain Length on Human Skin Barrier Recovery and Hydration

Abstract

Objective: To compare the effects of ceramide acyl chain length on human skin barrier function. Methods: Mixtures of phytoceramide containing non-hydroxy fatty acids (CER NPs) with different acyl chain lengths and corresponding test creams were prepared: C16–C24 CER NP and C24–C30 CER NP (ultra-long-chain, ULC CER NP). The content of C24 CER NP in these formulations was 0.3% and 39%, respectively. Liquid chromatography-tandem mass spectrometric (LC–MS/MS) analysis of skin ceramides was performed using tape-stripped human stratum corneum (SC) samples. A vehicle-controlled intra-subject human study was conducted to assess acute skin barrier recovery, skin hydration, and SC cohesion. Results: Levels of C24 and C26 ceramides were significantly increased in skin treated with C24-C30 CER NP. These analytical results were consistent with the findings from the human efficacy study. Functional evaluations demonstrated that C24–C30 CER NP significantly enhanced barrier recovery, skin hydration, and SC cohesion compared with C18 CER NP, whereas the C16–C24 CER NP formulation primarily improved skin hydration. Overall, the C24–C30 CER NP formulation exhibited the strongest barrier-enhancing effects among the tested formulations. Conclusion: This study provides the first in vivo human evidence that ceramides with longer acyl chains confer superior improvements in skin barrier function compared with shorter-chain ceramides. These findings highlight the critical role of acyl chain length in ceramide-mediated barrier enhancement and support the rational design of ceramide-based formulations for optimized skin barrier restoration. © 2026 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.