RT Journal Article T1 A lifestyle intervention with an energy-restricted Mediterranean diet and physical activity enhances HDL function: a substudy of the PREDIMED-Plus randomized controlled trial. A1 Sanllorente, Albert A1 Soria-Florido, María Trinidad A1 Castañer, Olga A1 Lassale, Camille A1 Salas-Salvadó, Jordi A1 Martínez-González, Miguel Ángel A1 Subirana, Isaac A1 Ros, Emilio A1 Corella, Dolores A1 Estruch, Ramón A1 Tinahones, Francisco J A1 Hernáez, Álvaro A1 Fitó, Montserrat K1 Mediterranean diet K1 calorie restriction K1 high-density lipoprotein K1 physical activity K1 randomized controlled trial AB Consumption of a Mediterranean diet, adequate levels of physical activity, and energy-restricted lifestyle interventions have been individually associated with improvements in HDL functions. Evidence of intensive interventions with calorie restriction and physical activity is, however, scarce. To determine whether an intensive lifestyle intervention with an energy-restricted Mediterranean diet plus physical activity enhanced HDL function compared to a non-hypocaloric Mediterranean eating pattern without physical activity. In 391 older adults with metabolic syndrome (mean age, 65 years; mean BMI, 33.3 kg/m2) from 1 of the Prevención con Dieta Mediterránea-Plus trial centers, we evaluated the impact of a 6-month intervention with an energy-restricted Mediterranean diet plus physical activity (intensive lifestyle; n = 190) relative to a nonrestrictive Mediterranean diet without physical activity (control; n = 201) on a set of HDL functional traits. These included cholesterol efflux capacity, HDL oxidative/inflammatory index, HDL oxidation, and levels of complement component 3, serum amyloid A, sphingosine-1-phosphate, triglycerides, and apolipoproteins A-I, A-IV, C-III, and E in apoB-depleted plasma. The intensive-lifestyle intervention participants displayed greater 6-month weight reductions (-3.83 kg; 95% CI: -4.57 to -3.09 kg) but no changes in HDL cholesterol compared with control-diet participants. Regarding HDL functional traits, the intensive lifestyle decreased triglyceride levels (-0.15 mg/g protein; 95% CI: -0.29 to -0.014 mg/g protein) and apoC-III (-0.11 mg/g protein; 95% CI: -0.18 to -0.026 mg/g protein) compared to the control diet, with weight loss being the essential mediator (proportions of mediation were 77.4% and 72.1% for triglycerides and apoC-III levels in HDL, respectively). In older adults with metabolic syndrome, an energy-restricted Mediterranean diet plus physical activity improved the HDL triglyceride metabolism compared with a nonrestrictive Mediterranean diet without physical activity. This trial is registered at isrctn.com as ISRCTN89898870. YR 2021 FD 2021 LK https://hdl.handle.net/10668/26964 UL https://hdl.handle.net/10668/26964 LA en DS RISalud RD Apr 8, 2025