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

Abstract

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 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]).

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: ISRCTN35739639.

Keywords: fatty acid; nutrition; sudden cardiac death.

Figure 1

Adjusted hazard ratios of total mortality by meeting the ISSFAL recommendation for a healthy ALA intake and PREvención con DIeta MEDiterránea (PREDIMED) intervention group. Data are given as hazard ratios. A multivariable Cox regression model was stratified for recruiting node and adjusted for age, sex, body mass index, current smoking status (never, former, or current smoker), physical activity (minutes at a given metabolic equivalent per day), total energy intake (kcal/day), history of diabetes (yes or no), history of hyperlipidemia (yes or no), history of hypertension (yes or no), alcohol intake (g/day), dietary factors (fiber, vegetables, fruits, and red meat), and meeting the ISSFAL recommendation of eicosapentaenoic acid and docosahexaenoic acid consumption for primary cardiovascular prevention (yes or no). Values for the “not meeting the recommendation” category are 1.00 (reference) for the low‐fat control diet group, 0.94 (95% CI, 0.73–1.23) for the MedDiet supplemented with nuts (MedDiet plus nuts) group, and 0.97 (95% CI 0.76–1.24) for the MedDiet supplemented with extra virgin olive oil (MedDiet plus EVOO). Values for the “meeting the recommendation” category are 0.81 (95% CI 0.52–1.25) for the control diet group, 0.71 (95% CI 0.47–1.06) for the MedDiet plus nuts group, and 0.59 (95% CI 0.36–0.96) for the MedDiet plus EVOO group. EVOO indicates extra virgin olive oil; ISSFAL, International Society for the Study of Fatty Acids and Lipids; MedDiet, Mediterranean diet.