Association of Higher Dietary Omega-3 Fatty Acid Intake With Cardiovascular-Kidney-Metabolic Syndrome Stage Severity and Mortality in US Adults: A Cross-Sectional and Prospective Cohort Analysis of NHANES 1999 to 2018

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome interlinks obesity, diabetes, kidney disease, and cardiovascular dysfunction. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) possess anti-inflammatory and metabolic properties potentially relevant to CKM health, yet their links to disease severity and mortality remain undefined. METHODS: This cross-sectional and longitudinal analysis included 27 934 US adults with CKM syndrome from NHANES (National Health and Nutrition Examination Survey) 1999 to 2018. Dietary n-3 PUFA intake (mg/kg per day) was ascertained from 2 24-hour recalls. Mortality was ascertained via linkage to the National Death Index through 2019. Cross-sectional CKM stage was analyzed using weighted ordered logistic regression. Mortality risk was evaluated using Cox models, restricted cubic splines, and weighted quantile sum regression. RESULTS: Each 10 mg/kg per day higher n-3 PUFA intake was associated with 13% lower odds of advanced CKM stage (odds ratio [OR], 0.87 [95% CI, 0.83-0.91]). Over a median 9-year follow-up (5150 deaths), a nonlinear, L-shaped relationship with all-cause mortality was observed, with a threshold at 22.35 mg/kg per day. Below this point, each 1 mg/kg per day increment was associated with a 1% lower mortality risk (hazard ratio [HR], 0.99 [95% CI, 0.98-1.00]). Participants in the highest versus lowest intake quartile had 48% lower odds of severe CKM stage (OR, 0.52 [95% CI, 0.46-0.60]) and 25% lower mortality (HR, 0.75 [95% CI, 0.61-0.92]). Docosapentaenoic acid was the primary n-3 PUFA species associated with mortality risk. Variation in glucose disposal and biological aging collectively explained 6.7% of the mortality association. CONCLUSIONS: Higher n-3 PUFA intake is associated with less severe CKM stage and linked to lower mortality in an L-shaped, threshold-dependent manner.