Changes in Resting Energy Expenditure in Response to Different Dietary Patterns: A Randomized Clinical Trial Exploratory Sub-Analysis

Background: Evidence comparing the effects of novel alternative dietary strategies on resting energy expenditure (REE) with a hypocaloric standard Mediterranean diet (MedDiet) with continuous caloric restriction remains limited. This study aimed to evaluate the effects of diets with varying ketogenic potentials—including a very-low-carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF)—on the REE of individuals with obesity compared to those of a standard MedDiet. Methods: This was a secondary post hoc sub-analysis of a three-month, parallel-arm, randomized clinical trial (RCT) including 160 adults with obesity (body mass index > 30 kg/m2). The participants were randomly assigned to one of five calorie-restricted dietary interventions: control (MedDiet), KD, early time-restricted eating (eTRE), late time-restricted eating (lTRE), or mADF. All interventions featured an individualized energy deficit of 600 kcal/day. In this sub-analysis, a total of 102 participants with valid baseline measures were included. The REE was assessed by indirect calorimetry, and longitudinal trajectories were evaluated using Linear Mixed Models (LMMs) in 98 participants to account for baseline variability and to maximize data retention. Results: The mean age of participants in this sub-analysis was 45.3 years (SD 10.8), and 73.1% were women. The longitudinal modeling confirmed no statistically significant differences in the adjusted REE trajectories among the five dietary groups over the 3-month intervention (Group × Time interaction, p = 0.506). Furthermore, the LMMs showed that total body weight (p < 0.001) and biological sex (p < 0.001) were the variables most strongly associated with REE within the model. No independent associations between circulating beta-hydroxybutyrate levels and REE trajectories were detected. Conclusions: Hypocaloric diets with varying macronutrient distributions and fasting windows did not show statistically significant differences in REE trajectories over the 3-month intervention. In this exploratory sub-analysis, the REE trajectories were more closely associated with individual biological characteristics, particularly body weight and sex, than with the specific dietary strategy employed. Given the modest sample size and exploratory nature of the study, these findings should be interpreted cautiously and require confirmation in larger, adequately powered prospective trials.