Dietary antioxidants and mortality in early-stage CKM syndrome: insights from NHANES

Cardiovascular-kidney-metabolic (CKM) syndrome is a newly recognized multisystem disorder, with over 90% of cases occurring in the early stages (0–3). However, there is a lack of evidence for dietary interventions during this phase. This study is the first to examine the connection between the composite dietary antioxidant index (CDAI) and mortality risk in early-stage CKM patients, aiming to support early intervention strategies based on nutrition. We analyzed data from 7,642 CKM 0–3 stage patients from the NHANES 2007–2018 cohort. Multivariable weighted Cox regression was used to assess the association between CDAI and all-cause/cardiovascular disease (CVD) mortality. A restricted cubic spline was applied to explore dose-response relationships, with subgroup analyses to explore population heterogeneity. During a median follow-up of 94 months, 594 all-cause deaths and 151 CVD deaths were recorded. Each unit increase in CDAI was substantially linked to a 6% decrease in all-cause mortality after controlling for covariates (HR = 0.94, 95% CI 0.91–0.98). Mortality risk was 40% lower in the highest CDAI quartile than in the lowest quartile (HR = 0.60, 95% CI 0.44–0.83). Dose-response analysis revealed a linear decreasing trend (p < 0.001). Subgroup analyses further supported these findings. Carotenoids and vitamin E were also substantially linked to a decreased all-cause mortality rate in CKM patients. For CVD mortality, a significant association was observed in unadjusted models (HR = 0.92, 95% CI 0.86–0.98, P < 0.05), but no significant association was found between CDAI and CVD mortality in the fully adjusted model (HR = 0.98, 95% CI 0.92–1.05, P = 0.62), suggesting potential mediation by covariates such as comorbidities and lifestyle factors. Enhanced dietary antioxidant capacity significantly reduces all-cause mortality risk in early-stage CKM patients (stages 0–3), with vitamin E and carotenoids potentially playing key protective roles. These findings provide dose-response evidence for early nutritional interventions in CKM syndrome, suggesting that multi-nutrient strategies targeting oxidative stress pathways may offer new directions for prevention and management.