Zinc bioavailability in alcohol-associated liver disease: Mechanisms and therapeutic implications

Abstract

Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide. Hepatic zinc deficiency is a consistent feature of ALD, yet the therapeutic efficacy of zinc supplementation remains limited. This review examines the causal role of zinc deficiency in ALD pathogenesis and highlights low zinc bioavailability as a key determinant in disease progression. We discuss the regulatory roles of zinc transporters (ZIPs, ZnTs), metallothioneins, and redox-sensitive ligands in maintaining zinc homeostasis. Furthermore, we introduce zinc-glutathione (ZnGSH) as a novel zinc formulation that improves intestinal absorption and hepatic utilization of zinc. Unlike conventional zinc salts, ZnGSH overcomes multiple physiological barriers to zinc uptake in ALD, offering enhanced bioavailability in both gut and liver tissues. Thus, supplementation with bioavailable zinc may present a promising therapeutic strategy for ALD and, potentially, also other chronic liver diseases.

Keywords: Alcohol-associated liver disease; Zinc deficiency; Zinc homeostasis; Zinc-glutathione.