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Am J Clin Nutr. 2017 Oct;106(4):973-983. doi: 10.3945/ajcn.116.151159. Epub 2017 Aug 16.

Plasma lipidomic profiles and cardiovascular events in a randomized intervention trial with the Mediterranean diet.

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Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
Navarra Institute for Health Research, Pamplona, Spain.
Biomedical Research Center in Physiopathology of Obesity and Nutrition, Carlos III Health Institute, Madrid, Spain.
Departments of Nutrition.
Epidemiology, and.
Broad Institute of MIT and Harvard, Cambridge, MA.
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA.
Department of Preventive Medicine, University of Valencia, Valencia, Spain.
Department of Preventive Medicine, University of Málaga, Málaga, Spain.
Institute of Health Sciences, University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain.
Departments of Internal Medicine and.
Endocrinology and Nutrition, August Pi i Sunyer Biomedical Research Institute Hospital Clinic, University of Barcelona, Barcelona, Spain.
Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain.
Cardiovascular and Nutrition Research Group, Hospital del Mar Medical Research Institute, Barcelona, Spain.
Department of Cardiology, University Hospital of Alava, Vitoria, Spain.
Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas, Spain.
Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA.
Human Nutrition Unit, Pere Virgili Institute for Health Research, Rovira i Virgili University, Reus, Spain; and.
Department of Medicine, Channing Division for Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain;


Background: Lipid metabolites may partially explain the inverse association between the Mediterranean diet (MedDiet) and cardiovascular disease (CVD).Objective: We evaluated the associations between 1) lipid species and the risk of CVD (myocardial infarction, stroke, or cardiovascular death); 2) a MedDiet intervention [supplemented with extra virgin olive oil (EVOO) or nuts] and 1-y changes in these molecules; and 3) 1-y changes in lipid species and subsequent CVD.Design: With the use of a case-cohort design, we profiled 202 lipid species at baseline and after 1 y of intervention in the PREDIMED (PREvención con DIeta MEDiterránea) trial in 983 participants [230 cases and a random subcohort of 790 participants (37 overlapping cases)].Results: Baseline concentrations of cholesterol esters (CEs) were inversely associated with CVD. A shorter chain length and higher saturation of some lipids were directly associated with CVD. After adjusting for multiple testing, direct associations remained significant for 20 lipids, and inverse associations remained significant for 6 lipids. When lipid species were weighted by the number of carbon atoms and double bonds, the strongest inverse association was found for CEs [HR: 0.39 (95% CI: 0.22, 0.68)] between extreme quintiles (P-trend = 0.002). Participants in the MedDiet + EVOO and MedDiet + nut groups experienced significant (P < 0.05) 1-y changes in 20 and 17 lipids, respectively, compared with the control group. Of these changes, only those in CE(20:3) in the MedDiet + nuts group remained significant after correcting for multiple testing. None of the 1-y changes was significantly associated with CVD risk after correcting for multiple comparisons.Conclusions: Although the MedDiet interventions induced some significant 1-y changes in the lipidome, they were not significantly associated with subsequent CVD risk. Lipid metabolites with a longer acyl chain and higher number of double bonds at baseline were significantly and inversely associated with the risk of CVD.


Mediterranean diet; PREDIMED; cardiovascular disease; lipids; metabolomics; randomized trial

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