Quercetin Intake and CKM Syndrome Risk: Dose-Response and Mechanistic Insights

Background/Objectives : Cardiovascular-kidney-metabolic (CKM) syndrome is a multisystem condition associated with oxidative stress. Flavonoids were studied individually, but not comprehensively in the CKM framework. This study aimed to explore associations between flavonoid intake and CKM risk and to investigate the underlying mechanisms. Methods : This study assessed the associations between dietary flavonoid intake and CKM risk using dose–response modeling based on National Health and Nutrition Examination Survey (NHANES) dietary data. Network pharmacology and molecular docking were employed to predict quercetin targets and validate binding affinity with the hub oxidative stress genes. Results : The advanced CKM group exhibited lower intakes of flavones, flavonols, kaempferol and quercetin compared to the nonadvanced group ( P < 0.05). Higher total flavonoids, flavonols and quercetin intake was associated with lower odds of advanced CKM stage. Nonlinear associations were observed, with intake levels corresponding to the lowest observed risk estimated at 449 mg/d for total flavonoids, 31 mg/d for flavonols, and 19 mg/d for quercetin. Eleven quercetin targets were identified; MPO and NOX4 were identified as oxidative stress candidates. Docking predicted binding affinities of − 9.4 and − 8.4 kcal/mol. Conclusions : Dietary quercetin intake is nonlinearly associated with lower odds of advanced CKM stage. These findings may suggest a potential role of quercetin in oxidative stress pathways via MPO and NOX4.