Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study
Authors: Sala‐Vila Aleix , Guasch‐Ferré Marta , Hu Frank B. , Sánchez‐Tainta Ana , Bulló Mònica , Serra‐Mir Mercè , López‐Sabater Carmen , Sorlí Jose V. , Arós Fernando , Fiol Miquel , Muñoz Miguel A. , Serra‐Majem Luis , Martínez J. Alfredo , Corella Dolores , Fitó Montserrat , Salas‐Salvadó Jordi , Martínez‐González Miguel A. , Estruch Ramón , Ros Emilio ,   the PREDIMED Investigators, Pérez‐Heras A. , Viñas C. , Casas R. , de Santamaría L. , Romero S. , Sacanella E. , Chiva G. , Valderas P. , Arranz S. , Baena J.M. , García M. , Oller M. , Amat J. , Duaso I. , García Y. , Iglesias C. , Simón C. , Quinzavos Ll. , Parra Ll. , Liroz M. , Benavent J. , Clos J. , Pla I. , Amorós M. , Bonet M.T. , Martin M.T. , Sánchez M.S. , Altirriba J. , Manzano E. , Altés A. , Cofán M. , Valls‐Pedret C. , Doménech M. , Gilabert R. , Bargalló N. , González R. , Molina C. , Márquez F. , Babio N. , Sorli M. , García Roselló J. , Diaz‐López A A. , Martin F. , Tort R. , Isach A. , Costa B. , Cabré J.J. , Fernández‐Ballart J. , Ibarrola‐Jurado N. , Alegret C. , Martínez P. , Millán S. , Piñol J.L. , Basora T. , Hernández J.M. , Toledo E. , Buil‐Cosiales P. , Ruiz‐Canela M. , Sanjulián B. , Díez‐Espino J. , Extremera‐Urabayen V. , García‐Arellano A. , Zazpe I. , Basterra‐Gortari F.J. , Goñi E , Razquin C. , Serrano‐Martínez M. , Bes‐Rastrollo M. , Gea A. , Martínez‐Lapiscina E.H. , Nuñez‐Córdoba J.M. , Arroyo‐Azpa C. , García‐Pérez L. , Villanueva‐Tellería J. , Cortés‐Ugalde F. , Sagredo‐Arce T. , García de la Noceda‐Montoy Mª D. , Vigata‐López Mª D. , Arceiz‐Campo Mª T. , Urtasun‐Samper A. , Gueto‐Rubio Mª V. , Churio‐Beraza B. , Lamuela‐Raventós Rosa M. , Castellote‐Bargallo A.I. , Medina‐Remón A. , Tresserra‐Rimbau A. , Carrasco P. , Ortega‐ Azorín C. , Asensio E.M. , Osma R. , Barragán R. , Francés F. , Guillén M. , González J.I. , Saiz C. , Portolés O. , Giménez F.J. , Coltell O. , Guillem‐Saiz P. , Quiles L. , Pascual V. , Riera C. , Pages M.A. , Godoy D. , Carratalá‐Calvo A. , Martín‐Rillo M.J. , Llopis‐Osorio E. , Ruiz‐ Baixauli J. , Bertolín‐Muñoz A. , Salaverría I. , del Hierro T. , Algorta J. , Francisco S. , Alonso A. , San Vicente J. , Sanz E. , Felipe I. , Alonso Gómez A. , Loma‐Osorio A. , García‐Valdueza M. , Moñino M. , Proenza A. , Prieto R. , Frontera G. , Ginard M. , Fiol F. , Jover A. , García J. , Covas M.I. , Tello S. , Vila J. , Schröder H. , De la Torre R , Muñoz‐Aguayo D. , Elosúa R. , Marrugat J. , Ferrer M. , Álvarez‐Pérez J. , DíazBenítez E. , Bautista‐Castaño I. , Maldonado‐Díaz I. , Sánchez‐Villegas A. , Castro I. , Henríquez P. , Ruano C. , Ortiz A. P. , Sarmiendo de la Fe F , Simón‐García C. , Falcón‐Sanabria I. , Macías‐Gutiérrez B. , Santana‐Santana A.J. , Gomez‐Gracia E. , Fernández‐Crehuet J. , Benítez Pont R. , Bianchi Alba M. , Wärnberg J. , Gómez‐Huelgas R. , Martínez‐González J. , Velasco García V. , de Diego Salas J , Baca Osorio A. , Gil Zarzosa J. , Sánchez Luque J.J. , Vargas López E. , Ruiz‐Gutierrez V. , Jurado Ruiz E. , Montero Romero E. , García García M. , Lapetra J. , Leal M. , Martínez E. , Santos J.M. , Ortega‐Calvo M. , Román P. , José García F. , Iglesias P. , Corchado Y. , Mayoral E. , Lama C. , Pintó X. , de la Cruz E , Galera A. , Soler Y. , Trias F. , Sarasa I. , Padres E. , Figueras R. , Solanich X. , Pujol R. , Corbella E. , Cabezas C. , Vinyoles E. , Rovira M.A. , García L. , Flores G. , Verdú J.M. , Baby P. , Ramos A. , Mengual L. , Roura P. , Yuste M.C. , Guarner A. , Rovira A. , Santamaría M.I. , Mata M. , de Juan C. , Brau A. , Marti A. , Mitjavila M.T. , Portillo M.P. , Sáez G. , Tur J. 
Published: January 2016

Background

Epidemiological 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).

Methods and Results

We longitudinally evaluated 7202 participants in the
PRE
vención con
DI
eta
MED
iterránea (
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]).

Conclusions

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.

Clinical Trial Registration

URL
:
http://www.Controlled-trials.com/
. Unique identifier:
ISRCTN
35739639.