Omega‐3 provides some benefit in cardiovascular‐kidney‐metabolic syndrome

In adults with cardiovascular‐kidney‐metabolic (CKM) syndrome, higher intake of omega‐3 polyunsaturated fatty acids (n‐3 PUFAs) has been associated with less severe CKM stage and lower mortality in new research.

Analyses of data from a large cohort of adults with CKM syndrome from the National Health and Nutrition Examination Survey showed that each 10 mg/kg-per-day increase in n‐3 PUFA intake was associated with 13-percent reduced odds of having an advanced CKM stage (odds ratio [OR], 0.87, 95 percent confidence interval [CI], 0.83–0.91; p<0.001). [J Am Heart Assoc 2026;doi:10.1161/JAHA.125.046079]

For all-cause mortality, a nonlinear L‐shaped relationship with n‐3 PUFA intake was observed, with a threshold at 22.35 mg/kg per day. Below this threshold, each 1 mg/kg-per-day increase in n‐3 PUFA intake was associated with a 1-percent risk reduction (hazard ratio [HR], 0.99, 95 percent CI, 0.98–1; p=0.008). Meanwhile, additional n‐3 PUFA intake above the 22.35 mg/kg-per-day threshold yielded no significant mortality benefit (HR, 1, 95 percent CI, 0.99–1.01; p=0.285).

When n‐3 PUFA intake was stratified into quartiles, patients in the highest vs lowest intake quartile had 48-percent reduced odds of having severe CKM stage (OR, 0.52, 95 percent CI, 0.46–0.60; p<0.001), 15-percent lower all-cause mortality (HR, 0.85, 95 percent CI, 0.73–0.99; p=0.023), and 20-percent lower noncardiovascular mortality (HR, 0.80, 95 percent CI, 0.67–0.94; p=0.005). 

Kaplan–Meier curves confirmed the all‐cause mortality benefit with the highest vs lowest quartile of dietary n‐3 PUFA intake in the entire population with CKM syndrome, as well as in the subgroups with CKM 1/2 stage and CKM3/4 stage (p<0.05 for all). Among subgroups, the all-cause and noncardiovascular mortality benefits were especially pronounced for patients who were <65 years of age (p=0.016) and those with higher physical activity levels (p=0.017).

“Collectively, these observational findings position n‐3 PUFAs as a modifiable dietary factor of interest for potentially modifying the CKM continuum. Clinically, targeted n‐3 PUFA supplementation could complement existing therapies, especially in early‐stage CKM,” according to the investigators.

They also pointed to the potential of increasing n‐3 PUFA intake for reducing mortality risk, particularly for patients with lower levels of consumption, for whom even modest increases in intake may lead to meaningful health benefits.

“Notably, docosapentaenoic acid (DPA) emerged as the predominant contributor to mortality risk reduction across all CKM stages (43.6 percent to 67.7 percent weight) … [highlighting] the underappreciated role of DPA, which may derive its efficacy from superior bioavailability and specialized proresolving mediator production,” the investigators said. “In contrast, eicosapentaenoic acid demonstrated stage‐specific cardiovascular protection (10.1 percent weight) in early CKM (stages 1–2).”

These data underscore the need to rethink the prevailing “one‐size‐fits‐all” approach to n‐3 PUFA supplementation and support stage‐specific dietary strategies tailored to CKM progression, they added.

The study included 27,934 adult patients (mean age 50.62 years, 50.34 percent male, 71.17 percent Non-Hispanic White) with CKM, of which 5,150 died over a median follow-up of 9 years. Nonsurvivors were more likely to use supplements (61.7 percent vs 55.6 percent; p<0.001), although they had 13–14-percent lower intake of n‐3/n‐6 PUFA compared with survivors.

A higher number of nonsurvivors than survivors had advanced CKM stages (3–4) (33.3 percent vs 8.7 percent; p<0.001) and used conventional lipid‐lowering therapy (33.2 percent vs 19.1 percent; p<0.001). Additionally, nonsurvivors had a lower estimated glucose disposal rate (5.77 vs 6.83 mg/kg per min; p<0.001) and accelerated biological ageing (1.60 vs 1.34 years; p=0.011) compared with survivors.

“Mechanistically, our mediation analyses indicate that improved glucose disposal (2.7 percent) and decelerated biological ageing (4 percent) partially explain the observed associations with mortality, aligning with dysregulated metabolic aging pathways in CKM,” the investigators said.

They called for further research to explore the interplay between n‐3 PUFAs, metabolic homeostasis, and biological ageing with the goal of optimizing personalized interventions.