6-gingerol modulates lipid metabolism, insulin resistance, and inflammation in NAFLD: evidence from a preclinical meta-analysis

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a major global health concern with limited effective pharmacological treatments. 6-Gingerol, a principal bioactive compound of ginger, has shown metabolic and hepatoprotective potential in experimental studies; however, its overall efficacy has not been systematically quantified.ObjectiveTo evaluate the effects of 6-gingerol on NAFLD-related outcomes in animal models and to explore potential sources of heterogeneity.MethodsA systematic review and meta-analysis of controlled animal studies was conducted in accordance with PRISMA guidelines. Multiple databases were searched to identify relevant studies. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using random-effects models. Prespecified subgroup analyses were performed based on species, dose, and treatment duration, and sensitivity analyses assessed the robustness of the results.ResultsEight studies were included. 6-Gingerol significantly improved anthropometric indices, hepatic and circulating lipid profiles, liver enzymes, and glucose metabolism parameters. Beneficial effects were also observed for inflammatory mediators and adipokines in a subset of studies. Despite moderate to high heterogeneity, favorable effects were observed across the evaluated major outcome domains. Exploratory subgroup analyses suggested that treatment duration, dose, and species may contribute to between-study variability; however, the small number of studies within several subgroup strata precluded firm conclusions regarding effect modification. Sensitivity analyses showed that the overall direction of the pooled estimates was not materially changed by removal of individual studies.Conclusion6-Gingerol was associated with favorable changes in several metabolic and hepatic outcomes in animal models of NAFLD. However, these findings should be interpreted cautiously because of the limited number of studies, substantial heterogeneity, and incomplete methodological reporting. Further standardized preclinical and clinical studies are warranted.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261290223, identifier CRD420261290223.