Are the ratio and amount of n-6 and n-3 fatty acids associated with cardiovascular outcomes?—a GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials

Although some meta-analyses evaluated the risk of cardiovascular biomarkers and the ratio of dietary n-6 and n-3 fatty acids (FAs), few meta-analyses of randomized controlled trials were focused on the relationship between the risk of cardiovascular outcome and the dietary n-6/n-3 FA ratio. This meta-analysis can provide a more direct indication (cardiovascular outcome) for cardiovascular disease than biomarkers. In addition to ratio, the absolute amounts of dietary n-6, n-3 fatty acids and total dietary fat should be considered in this association. Therefore, a dose-response meta-analysis and systematic review were performed. The Cochrane databases, Web of Science, PubMed and Embase were searched in August 2023. Randomized controlled trials that investigated the association between the ratio of n-6/n-3 FA, dietary fat, n-6 FAs or n-3 FAs and cardiovascular disease, coronary heart disease, myocardial infarction, or stroke in adults without other diseases were included. The results showed that higher n-6/n-3 FA was associated with all cardiovascular outcomes when n-3 FA was higher than 1 g/d (1.08, 1.00 to 1.18). Per 500 mg/d increment of n-3 FA was related to a 3% lower risk of 0.97 in cardiovascular events. N-6 FA intake was curvilinearly associated with cardiovascular mortality (P=0.0094). Thus, a lower n-6/n-3 FA ratio (<7) of diet may be promoted from the above results for cardiovascular disease prevention, including higher n-3 FAs (＞1g/d).