title: Long-Term Immunomodulatory Effects of a Mediterranean Diet in Adults at High Risk of Cardiovascular Disease in the PREvención con DIeta MEDiterránea (PREDIMED) Randomized Controlled Trial.
abstract: The Mediterranean diet (MedDiet) has demonstrated short-term anti-inflammatory effects, but little is known about its long-term immunomodulatory properties.
  
  
  
  Our goal was to assess the long-term effects of the MedDiet on inflammatory markers related to atherogenesis in adults at high risk of cardiovascular disease (CVD) compared with the effects of a low-fat diet (LFD).
  
  
  
  We randomly assigned 165 high-risk participants (one-half men; mean age: 66 y) without overt CVD to 1 of 3 diets: a MedDiet supplemented with extra-virgin olive oil, a MedDiet supplemented with nuts, or an LFD. Follow-up data were collected at 3 and 5 y. Repeated-measures ANOVA, adjusted for potential confounding variables, was used to evaluate changes in diet adherence, CVD risk factors, and inflammatory variables.
  
  
  
  The 2 MedDiet groups achieved a high degree of adherence to the intervention, and the LFD group had reduced energy intake from fat by 13% by 5 y. Compared with baseline, at 3 and 5 y, both MedDiet groups had significant reductions of ≥16% in plasma concentrations of high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor α, and monocyte chemoattractant protein 1 (P ≤ 0.04), whereas there were no significant changes in the LFD group. The reductions in CD49d and CD40 expressions in T lymphocytes and monocytes at 3 y were ≥16% greater in both MedDiet groups than were the changes in the LFD group (P < 0.001) at 3 y. Compared with baseline, at 3 y, the MedDiet groups had increased HDL-cholesterol (≥8%) and decreased blood pressure (>4%) and total cholesterol, LDL-cholesterol, and triglyceride (≥8%) concentrations. At 5 y, concentrations of glucose (13%) and glycated hemoglobin (8%) had increased with the LFD.
  
  
  
  The MedDiet participants had lower cellular and plasma concentrations of inflammatory markers related to atherosclerosis at 3 and 5 y. This anti-inflammatory role of the MedDiet could explain in part the long-term cardioprotective effect of the MedDiet against CVD. This trial was registered at controlled-trials.com as ISRCTN35739639.
authors.affiliation: Department of Internal Medicine, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute, University of Barcelona, Barcelona, Spain; CIBEROBN Fisiopatología de la Obesidad y Nutrición (Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III (Carlos III Health Institute), Madrid, Spain;
authors.forename: Rosa
authors.initials: R
authors.lastname: Casas
authors.affiliation: Department of Internal Medicine, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute, University of Barcelona, Barcelona, Spain; CIBEROBN Fisiopatología de la Obesidad y Nutrición (Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III (Carlos III Health Institute), Madrid, Spain; esacane@clinic.ub.es.
authors.forename: Emilio
authors.initials: E
authors.lastname: Sacanella
authors.affiliation: Department of Nutrition and Food Science School of Pharmacy, University of Barcelona, Barcelona, Spain;
authors.forename: Mireia
authors.initials: M
authors.lastname: Urpí-Sardà
authors.affiliation: CIBEROBN Fisiopatología de la Obesidad y Nutrición (Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III (Carlos III Health Institute), Madrid, Spain; Department of Epidemiology and Department of Biochemistry and Molecular Biology, School of Medicine, University of Valencia, Valencia, Spain;
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.affiliation: CIBEROBN Fisiopatología de la Obesidad y Nutrición (Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III (Carlos III Health Institute), Madrid, Spain; Cardiovascular Risk and Nutrition and REGICOR research group, Hospital del Mar Medical Research Institute, Barcelona, Spain;
authors.forename: Olga
authors.initials: O
authors.lastname: Castañer
authors.affiliation: CIBEROBN Fisiopatología de la Obesidad y Nutrición (Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III (Carlos III Health Institute), Madrid, Spain; Department of Nutrition and Food Science School of Pharmacy, University of Barcelona, Barcelona, Spain;
authors.forename: Rosa-María
authors.initials: RM
authors.lastname: Lamuela-Raventos
authors.affiliation: CIBEROBN Fisiopatología de la Obesidad y Nutrición (Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III (Carlos III Health Institute), Madrid, Spain; Human Nutrition Unit, Hospital Universitari de Sant Joan de Reus, IISPV, Universitat Rovira i Virgili, Reus, Spain;
authors.forename: Jordi
authors.initials: J
authors.lastname: Salas-Salvadó
authors.affiliation: CIBEROBN Fisiopatología de la Obesidad y Nutrición (Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III (Carlos III Health Institute), Madrid, Spain; Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, Pamplona, Spain; and.
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Martínez-González
authors.affiliation: CIBEROBN Fisiopatología de la Obesidad y Nutrición (Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III (Carlos III Health Institute), Madrid, Spain; Lipid Clinic, Service of Endocrinology and Nutrition, Institut d'Investigació Biomèdica August Pi i Sunyer, Hospital Clinic, Barcelona, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Ros
authors.affiliation: Department of Internal Medicine, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute, University of Barcelona, Barcelona, Spain; CIBEROBN Fisiopatología de la Obesidad y Nutrición (Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III (Carlos III Health Institute), Madrid, Spain;
authors.forename: Ramon
authors.initials: R
authors.lastname: Estruch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000517:prevention & control*; D018752:Diet, Fat-Restricted; D038441:Diet, Mediterranean; D002149:Energy Intake; D015444:Exercise; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009754:Nuts; D000069463:Olive Oil / Q000008:administration & dosage; D012307:Risk Factors; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; D000069463:Olive Oil
keywords: Mediterranean diet; adhesion molecules; cardiovascular disease; inflammation; long-term; peripheral blood mononuclear cells