Associations Between n-3 and n-6 Polyunsaturated Fatty Acids and Stroke Risk, Mediated by the Dietary Inflammatory Index: Evidence from NHANES 2007-2018

OBJECTIVE: This study aimed to explore the associations between polyunsaturated fatty acids (PUFAs), inflammatory biomarkers, and stroke risk, and to assess the mediating role of the dietary inflammatory index (DII). METHODS: Data from 26,556 participants in National Health and Nutrition Examination Survey (NHANES) 2007-2018 were analyzed. Weighted logistic regression models were used to examine the relationships between n-3 PUFAs, n-6 PUFAs, inflammatory biomarkers, and stroke risk. Propensity score matching (PSM) was applied to match stroke and non-stroke participants in a 1:2 ratio. Restricted cubic spline (RCS) analysis assessed non-linear associations between PUFAs, DII, and stroke risk, and mediation analysis explored the role of DII in the PUFAs-stroke relationship. Subgroup analyses were conducted to assess effect modification by demographic and clinical variables. RESULTS: Of the 26,556 participants, 1,022 (3.85%) reported a stroke diagnosis. PSM was conducted to generate a balanced cohort of 1,021 stroke cases and 2,040 non-stroke controls. Before PSM, higher intake (Q3 and Q4) of n-3 and n-6 PUFAs was significantly inversely correlated with stroke risk. After PSM, in the fully adjusted model, the fourth quartiles of n-3 and n-6 PUFAs remained negatively associated with stroke, with ORs of 0.72 (95%CI: 0.53-0.97, P for trend = 0.001) and 0.63 (95%CI: 0.47-0.86, P for trend < 0.001), respectively. Conversely, the highest quartile of DII and neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) remained positively associated with stroke, with an OR of 1.66 (95%CI: 1.24-2.24, P for trend < 0.001) and 1.46 (95%CI: 1.07-2.00, P for trend = 0.002). Stroke risk gradually decreased alongside elevated n-3 PUFA concentrations below the threshold values of 34.44 mg/kg/day (pre-PSM) and 35.71 mg/kg/day (post-PSM), and trended upward when exceeding these critical levels. Mediation analysis suggested DII significantly mediated the effects of n-3 PUFAs (P = 0.02) and n-6 PUFAs (P < 0.01) on stroke after PSM. A significant interaction was observed between n-6 PUFAs and poverty income ratio (PIR) (P for interaction = 0.006). CONCLUSIONS: The Q4 of both n-3 and n-6 PUFAs are inversely associated with stroke risk. The nonlinear, biphasic relationship observed between n-3 PUFAs intake and stroke risk. DII's mediating role underscores the importance of dietary inflammation in managing stroke risk.