Composite Dietary Antioxidant Index and Mortality Reduction in CKM Stages 0-3: Stratified Benefits for Low-Oxidative Burden Subgroups

Abstract Background: Cardiovascular-kidney-metabolic (CKM) syndrome represents a growing public health challenge. Readily accessible and modifiable dietary factors, particularly antioxidant intake, deserve attention in mitigating disease progression. This study examines the association between the Composite Dietary Antioxidant Index (CDAI) and mortality across CKM stages 0–3, aiming to identify actionable dietary strategies for population-level impact. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2001–2018 (n = 16,838 adults) were analyzed. Participants were grouped into CDAI tertiles (low, middle, high). Weighted Cox proportional hazards models estimated hazard ratios (HRs) for mortality, adjusted for demographic, socioeconomic, behavioral, and clinical covariates. Kaplan-Meier survival curves and restricted cubic spline analyses were performed. Results: High CDAI participants exhibited significantly lower all-cause mortality compared to the low CDAI group (HR = 0.80, 95% CI: 0.66–0.97, p-trend = 0.02). Cancer mortality also trended lower (HR = 0.69, 95% CI: 0.48-1.00, p = 0.05). A nonlinear inverse relationship between CDAI and all-cause mortality was observed (p-nonlinearity = 0.02), with protective effects more pronounced in individuals aged < 65, males, those with higher education, non-hypertensives, and never-smokers, with a significant interaction observed for smoking (p-interaction = 0.02). Conclusions: Higher dietary antioxidant intake is associated with reduced all-cause and cancer mortality among U.S. adults with CKM stages 0–3, exhibiting a dose-dependent relationship. Antioxidant-rich diets may have greater benefit in early-stage CKM, particularly in those with lower oxidative burden. These findings warrant further prospective and interventional studies.