Final Report Summary - PREDIMED PLUS (Long-term effects of an energy-restricted Mediterranean diet on mortality and cardiovascular disease: the PREDIMED PLUS Study) The PREDIMED-Plus design and methods are described elsewhere (Martínez-González et al, 2019). Briefly, PREDIMED-Plus is a multicenter, randomized, single-blinded clinical trial evaluating the effects of a special intervention including: a) energy-reduced MedDiet (er-MedDiet); b) physical activity; and c) a behavioral therapy for weight loss. The control group was randomly allocated to usual care with a traditional MedDiet, without any energy restriction, no physical activity intervention and no special goals for weight loss.Participants were 6,874 men and women aged 55 to 75 and 60 to 75 years, respectively, free from CVD at baseline, with initial BMI between 27-40 kg/m2 and with metabolic syndrome. They were recruited (2013-2016) in 23 Spanish centers working in 208 primary care clinics of the National Health System. For participants randomly allocated to the intervention group (IG), trained and certified dietitians delivered three interventions per month during the first year (a group session, an individual motivational interview and a phone call). Participants in the control group (CG) received instructions on the traditional MedDiet and general lifestyle recommendations for managing the metabolic syndrome. Every six months, control group participants were invited to participate in group sessions led by dietitians. All participants were provided with an allotment of extra-virgin olive oil (one liter per month) and nuts (500 g per month) at no cost for them. A validated 143-item FFQ was collected at baseline and repeatedly after 6 and 12 months. Spanish food-composition tables were used to derive energy and nutrient intake. An additional 17-item questionnaire assessing adherence to an er-MedDiet was a decisive tool used to foster adherence to the intended dietary changes in the IG and it was administrated to both groups. Mixed-effect linear models were used to assess changes in nutritional variables and risk factors from baseline to 6 and 12 months of intervention. The control and intervention groups were well balanced at randomization showing similar baseline characteristics. Participants in the CG relatively improved their adherence to the er-MedDiet in +20% and +23%, after 6- and 12-month intervention, respectively. In comparison, relative improvements in adherence within the IG were 48% after 6 months and 51% after 12 months. The greatest reductions in food consumption after 12 months of intervention were observed for refined olive oil (IG: -67% vs CG: -62%), pastries (IG: -57% vs CG: -33%), refined grains (IG: -56% vs CG: -24%), and whole-fat dairy (IG: -44% vs CG: -28%). And the greatest increases were observed for the consumption of tree nuts (IG: 101% vs CG: 75%), whole grains (IG: 67% vs CG: 20%), and extra virgin olive oil (IG: 33% vs CG: 38%). The greatest between-group differences were observed for a higher increment in the consumption of vegetables in the IG than in the CG [+206 (95%CI: +153 to +259)], and also for fruits [+192 (95%CI: +113 to +271) g/wk], whole-grain cereals [+165 (95% CI: +138 to +191)] and low-fat dairy [+266 (95%CI: +202 to +329). Conversely, a significantly reduced consumption in the IG vs. the CG was attained for refined grains [-302 (95%CI: -333 to -270)]. Significant between-group differences at 6-month and 1-year were observed for weight, waist, lipids, systolic and diastolic blood pressure, blood glucose and glycated hemoglobin (HbA1c). One-year weight loss showed between-group differences of -2.9 kg (95% CI: -3.1 to -2.7). One-year between-group differences in changes were -9.8 mg/dl (-13.2 to -6.4) for triglycerides, 2.6 mg/dl (-3.7 to -1.5) for fasting blood glucose and -0.11% (-0.14 to -0.07) for HbA1c. Final results including hard cardiovascular end-points will be available after 2022.Martínez-González MA, et al. Cohort Profile: Design and methods of the PREDIMED-Plus randomized trial. Int J Epidemiol. 2018Nov 22. [Epub ahead of print] PMID: 30476123.