Sanllorente, AlbertSoria-Florido, María TrinidadCastañer, OlgaLassale, CamilleSalas-Salvadó, JordiMartínez-González, Miguel ÁngelSubirana, IsaacRos, EmilioCorella, DoloresEstruch, RamónTinahones, Francisco JHernáez, ÁlvaroFitó, Montserrat2025-01-072025-01-072021https://hdl.handle.net/10668/26964Consumption 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.enMediterranean dietcalorie restrictionhigh-density lipoproteinphysical activityrandomized controlled trialAgedDiet, MediterraneanExerciseFemaleHumansLife StyleLipoproteins, HDLMaleMetabolic SyndromeMiddle AgedTriglyceridesresearch article34582548open access10.1093/ajcn/nqab2461938-3207https://academic.oup.com/ajcn/article-pdf/114/5/1666/41105370/nqab246.pdf