Therapeutic Potential of Flavonoids and Their Metabolites in Hyperlipidaemia: Molecular Mechanisms, Bioavailability and Clinical Perspectives.

Abstract

Hyperlipidaemia is a major modifiable risk factor for cardiovascular disease and remains a global health concern. Although conventional lipid-lowering drugs are effective, their long-term use is often associated with adverse effects, prompting interest in safer dietary alternatives. Flavonoids, such as quercetin, naringenin, and catechins, have gained attention for their hypolipidemic and cardioprotective properties. This narrative review summarizes the current evidence on the therapeutic potential of quercetin, catechins, naringenin, and their bioactive metabolites in the management of hyperlipidaemia. The literature was identified through comprehensive searches of PubMed, Scopus, Web of Science, and Google Scholar for studies published between 2015 and March 2026 using combinations of the keywords flavonoids, quercetin, catechins, naringenin, metabolites, hyperlipidaemia, dyslipidaemia, lipid metabolism, cardiovascular disease, and gut microbiota. Original research articles, clinical studies, experimental investigations, and high-quality review articles published in English were considered, while duplicate, non-English, and unrelated reports were excluded from the study. Evidence indicates that flavonoids and their metabolites modulate multiple pathways involved in lipid homeostasis, including the inhibition of HMG-CoA reductase, activation of AMPK and PPARα, suppression of SREBP-1c, enhancement of LDL receptor expression, regulation of gut microbiota, and attenuation of oxidative stress and inflammation. Despite encouraging preclinical and clinical findings, limited bioavailability, extensive metabolism, inter-individual variability, and insufficient long-term clinical evidence remain important challenges. Overall, flavonoids and their metabolites represent promising adjunctive dietary strategies for improving lipid metabolism and reducing cardiovascular risk. However, welldesigned randomized clinical trials and advanced delivery systems are needed to establish their therapeutic efficacy and clinical applicability.