Safety and Efficacy of Tripalmitoleoylglycerol in Dermatitis: A Randomized Controlled Trial

Overview

This randomized, double-blind, placebo-controlled clinical trial is designed to evaluate the safety and efficacy of topical palmitoleic acid glyceride supplementation in improving skin barrier impairment associated with chronic dermatitis, with a particular focus on the interaction between physical activity, skin microbiota, and lipid metabolism. Emerging evidence suggests that regular physical activity reshapes the skin microenvironment, including alterations in sebaceous lipid composition and enrichment of Staphylococcus epidermidis, which possesses lipase activity capable of metabolizing glycerides into bioactive fatty acids. Palmitoleic acid, a key lipid metabolite derived from palmitoleic acid glycerides, has demonstrated anti-inflammatory and barrier-protective properties in preclinical and clinical settings. However, it remains unclear whether restoring exercise-associated lipid metabolites through topical application can improve skin barrier dysfunction in individuals with chronic dermatitis, and whether physical activity status modifies therapeutic efficacy. Research Objectives： 1. Does topical application of low-concentration palmitoleic acid glyceride improve skin barrier function, as measured by transepidermal water loss (TEWL), in individuals with chronic dermatitis? 2. Does physical activity status influence the therapeutic response to palmitoleic acid glyceride treatment? 3. Are improvements in skin barrier function associated with changes in skin microbiota composition, microbial lipase activity, and lipid metabolism at the skin surface? Study Design and Group Allocation： Eligible male participants aged 18-59 years with clinical manifestations of chronic dermatitis and evidence of skin barrier impairment will be enrolled. Based on physical activity levels defined according to World Health Organization guidelines, participants will be stratified into physically inactive/insufficiently active and physically active/highly active groups. Within each stratum, participants will be randomly assigned in a 1:1 ratio to receive either topical palmitoleic acid glyceride or placebo, resulting in four study groups: 1. Inactive Placebo Group: No regular physical activity; topical placebo. 2. Inactive Intervention Group: No regular physical activity; topical palmitoleic acid glyceride. 3. Active Placebo Group: Regular moderate-intensity aerobic activity; topical placebo. 4. Active Intervention Group: Regular moderate-intensity aerobic activity; topical palmitoleic acid glyceride. Participant Procedures： 1. Daily topical application of either 0.5% palmitoleic acid glyceride or placebo to a predefined skin lesion area for 7 consecutive days. 2. Non-invasive assessment of skin barrier function, including TEWL measurements, at baseline and after completion of the intervention. 3. Clinical evaluation of skin symptoms, including erythema, scaling, and pruritus, using standardized scoring systems (PASI or SCORAD, as appropriate). 4. Collection of skin swab samples for microbiome and metabolomic analyses to assess microbial lipase activity and palmitoleic acid production. 5. A subset of participants will undergo skin biopsy for histological and immunohistochemical analyses. 6. Weekly follow-up assessments to monitor treatment adherence and record any adverse events, particularly local skin reactions. This study seeks to elucidate a novel exercise-microbiota-lipid axis in skin barrier regulation and to provide translational evidence for metabolite-based therapeutic strategies in chronic inflammatory skin diseases.