Therapeutic Effects of Dihydromyricetin on Wholly Alcohol-Attributed Conditions: A Systematic Review

Background: Alcohol use is a major global health burden and is causally linked to several wholly alcohol-attributed conditions, including alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). Current therapeutic options remain limited. Dihydromyricetin (DHM), a plant-derived flavonoid with antioxidant and anti-inflammatory properties, has emerged as a potential candidate for mitigating alcohol-induced toxicity. This systematic review aimed to comprehensively evaluate the therapeutic effects of DHM across alcohol-related conditions. Methods: A systematic literature search was conducted in PubMed from inception through December 2025 for studies investigating the effects of DHM or DHM-containing extracts on alcohol-related outcomes. Both preclinical (in vitro and in vivo) and clinical studies were considered. Study quality was assessed qualitatively due to heterogeneity precluding use of a standardized risk-of-bias tool. Results were synthesized narratively by outcome category; meta-analysis was not performed. This review was unregistered with no prior protocol. Results: A total of 22 studies were included, comprising 8 in vitro, 17 in vivo, and 2 clinical studies, with some studies contributing data to more than one category. Across models, DHM consistently attenuated ethanol-induced cytotoxicity, oxidative stress, inflammation, and hepatic steatosis. DHM improved liver injury biomarkers (e.g., AST and ALT), enhanced antioxidant defenses, and modulated key signaling pathways including Nrf2 and AMPK. Additionally, DHM supported mitochondrial function and intestinal barrier integrity. However, findings related to ethanol metabolism and neurobehavioral outcomes were inconsistent. Clinical evidence was limited to two small trials using Hovenia dulcis extracts, which demonstrated reductions in hangover severity and selected inflammatory markers but did not directly evaluate isolated DHM. Conclusions: DHM demonstrates robust preclinical efficacy in mitigating alcohol-induced injury, particularly in hepatic outcomes. Despite promising mechanistic and experimental evidence, clinical data remain limited. The certainty of evidence is constrained by preclinical study heterogeneity, the absence of formal risk-of-bias assessment, and the lack of clinical trials using isolated DHM. Well-designed clinical trials using standardized DHM formulations are needed to establish its complete therapeutic potential in alcohol-related disorders.