Sala-Vila, AleixGuasch-Ferré, MartaHu, Frank BSánchez-Tainta, AnaBulló, MònicaSerra-Mir, MercèLópez-Sabater, CarmenSorlí, Jose VArós, FernandoFiol, MiquelMuñoz, Miguel ASerra-Majem, LuisMartínez, J AlfredoCorella, DoloresFitó, MontserratSalas-Salvadó, JordiMartínez-González, Miguel AEstruch, RamónRos, EmilioPREDIMED InvestigatorsB,2023-01-252023-01-252016-01-26http://hdl.handle.net/10668/9778Epidemiological evidence suggests a cardioprotective role of α-linolenic acid (ALA), a plant-derived ω-3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω-3 fatty acids (long-chain n-3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all-cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long-chain n-3 polyunsaturated fatty acids (≥500 mg/day). We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable-adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9-y follow-up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56-0.92) for all-cause mortality and 0.95 (95% CI 0.58-1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long-chain n-3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67-1.05) for all-cause mortality, 0.61 (95% CI 0.39-0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29-0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22-1.01) for sudden cardiac death. The highest reduction in all-cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45-0.87]). In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all-cause mortality, whereas protection from cardiac mortality is limited to fish-derived long-chain n-3 polyunsaturated fatty acids. URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/fatty acidnutritionsudden cardiac deathAgedAged, 80 and overCardiovascular DiseasesChi-Square DistributionDietFatty Acids, Omega-3FemaleHumansJuglansLongitudinal StudiesMaleMiddle AgedMultivariate AnalysisNutritive ValueNutsOlive OilProportional Hazards ModelsProspective StudiesProtective FactorsRisk AssessmentRisk FactorsRisk Reduction BehaviorSeafoodSpainTime Factorsalpha-Linolenic Acidresearch article26813890open access10.1161/JAHA.115.0025432047-9980PMC4859371https://www.ahajournals.org/doi/pdf/10.1161/JAHA.115.002543https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859371/pdf