Long-Term Immunomodulatory Effects of a Mediterranean Diet in Adults at High Risk of Cardiovascular Disease in the PREvencion con Dleta MEDiterranea (PREDIMED) Randomized Controlled Trial

Background: The Mediterranean diet (MedDiet) has demonstrated short-term anti-inflammatory effects, but little is known about its long-term immunomodulatory properties. Objective: 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). Methods: 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. Results: 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 alpha, 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. Conclusions: 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.