Effects of Isocaloric Early vs. Late Time-Restricted Eating on Insulin Sensitivity, Cardiometabolic Health, and Internal Circadian Time in Women with Overweight or Obesity: A Randomized Clinical Trial

IMPORTANCE It is unclear whether time-restricted eating (TRE) induces cardiometabolic benefits independently of the reduction in calorie intake and whether its effects depend on the timing of the eating window. OBJECTIVE The main objective was to determine whether 8-hour TRE alters insulin sensitivity in an isocaloric setting. The secondary objective was to compare effects of early (eTRE) vs. late TRE (lTRE) on cardiometabolic outcomes and internal circadian time. DESIGN, SETTING, AND PARTICIPANTS The study was a randomized 10-week crossover trial conducted at the German Institute of Human Nutrition Potsdam-Rehbruecke, Germany, between March 2020 to December 2021. Participants were non-diabetic women with overweight or obesity, aged 18 to 70 years. INTERVENTIONS All participants underwent two 2-week isocaloric interventions with a restriction of the eating period to 8 hours: (i) early in the day (eTRE: 8:00-16:00 hr) and (ii) late in the day (lTRE: 13:00-21:00 hr). MAIN OUTCOMES AND MEASURES The primary outcome was insulin sensitivity assessed by an oral glucose tolerance test. Secondary outcomes included levels of glucose, lipids, adipokines, cytokines, oxidative stress markers, and internal circadian phase. RESULTS 31 female participants (mean (SD) BMI of 30.5 (2.9) and median [IQR] age of 62 [53-65] years) completed the trial. Timely adherence was 96.5 % in eTRE and 97.7 % in lTRE. Food records showed a minor daily calorie deficit in eTRE (-167 kcal) but not in lTRE. Insulin sensitivity did not differ between eTRE and lTRE (-0.07; 95% CI, -0.77 to 0.62, P = .83) and showed no within-intervention changes (eTRE: 0.31; 95% CI, -0.14 to 0.76, P = .11; lTRE: 0.19; 95% CI, -0.22 to 0.60, P = .25). 24-hour glucose levels, lipid, inflammatory, and oxidative stress markers showed no clinically meaningful between- and within-intervention differences. lTRE delayed the circadian phase in blood monocytes (24 min; 95% CI, -5 to 54 min, P = .10) and sleep midpoint (15 min; 95% CI, 7 to 22 min, P = .001) compared to eTRE. CONCLUSIONS AND RELEVANCE In a nearly isocaloric setting, neither eTRE nor lTRE improve insulin sensitivity or other cardiometabolic traits despite significant changes in the circadian system.