Protective Effects of Allicin and Garlic-Derived Interventions Against Metabolic Dysfunction-Associated Steatotic...

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and poses a significant public health challenge. Allicin, a major bioactive organosulfur compound derived from garlic, has emerged as a promising candidate for MASLD prevention and management due to its antioxidant, anti-inflammatory, and metabolic regulatory properties. Despite its potential, evidence regarding allicin's efficacy on MASLD remains limited and heterogeneous because existing studies have evaluated different garlic-derived interventions across diverse experimental settings. This review therefore distinguishes studies of purified allicin from those of raw garlic, garlic powder, aged garlic extract, black garlic, garlic essential oil, and individual garlic compounds. Preclinical studies using allicin suggest beneficial effects on hepatic steatosis, inflammation, glucose homeostasis, and lipid metabolism. Human studies, however, have evaluated raw garlic consumption or garlic powder supplementation rather than allicin alone. Findings from other garlic preparations and individual compounds are attributed only to the intervention tested, because differences in composition, stability, bioavailability, metabolism, and pharmacological activity preclude their attribution to allicin. Moreover, the available clinical trial evidence comprises five publications derived from only two randomized controlled trials conducted in Iran, both lasting 12-15 weeks. In addition, preclinical evidence most consistently supports regulation of hepatic lipid metabolism, particularly the AMP-activated protein kinase/sterol regulatory element-binding protein-1c-related signaling, as a potential mechanism underlying the anti-steatotic effects of allicin. Additional pathways may involve inflammatory signaling, oxidative stress, gut microbiota, and bile acid-related regulation, although the evidence for several of these mechanisms remains suggestive. Nevertheless, the precise molecular targets and signaling networks underlying these effects remain incompletely understood, and the relevance of allicin to aging-related MASLD is largely unexplored because previous studies have used young animals. Future studies should incorporate aged models and long-term randomized controlled trials across diverse populations to clarify the mechanisms, therapeutic potential, and safety of allicin in MASLD.