Time-restricted eating, liver health, and fecal microbiota in adults with overweight or obesity: A randomized controlled trial

BACKGROUND AND AIMS: The optimal eating window for time-restricted eating (TRE) remains unclear. We investigated the effects of 8-hour TRE combined with usual care (UC, a Mediterranean diet-based education program), versus UC alone over 12 weeks on hepatic fat fraction, liver health markers, and fecal microbiota in adults with overweight or obesity. METHODS: In this multicenter randomized trial, participants (50% women) were assigned to UC (n=49), early TRE (n=49), late TRE (n=52), or self-selected TRE (n=47). Hepatic fat fraction was assessed by MRI; liver markers included elastography-based parameters, liver enzymes, and circulating biomarkers. Fecal microbiota was analyzed by 16S rRNA gene sequencing. RESULTS: Hepatic fat fraction decreased significantly within the three TRE groups (all P≤0.02), but no between-group differences were observed when comparing early TRE (mean difference [MD]: -0.4%; P=0.95), late TRE (MD: -1.5%; P=0.15), and self-selected TRE groups (MD: -0.7%; P=0.77) with the UC group, or among the TRE groups themselves (all P≥0.41). Similarly, no between-group differences were found in liver health markers and fecal microbiota. Participants with metabolic dysfunction-associated steatotic liver disease at baseline as well as those achieving ≥5% weight loss had greater reductions in hepatic fat fraction than those who did not (MD: -2.7 and -2.6%; respectively, both P<0.001). A higher proportion of participants in the TRE groups achieved ≥5% weight loss compared with UC (41-44% vs 16%; P=0.001). CONCLUSIONS: These findings suggest that the timing of the eating window in TRE may not impact hepatic fat fraction or microbiota composition beyond the effects of weight loss, though the study was not powered for secondary outcomes. CLINICAL TRIALS REGISTRATION: The study was registered on ClinicalTrials.gov (identifier: NCT05310721). CLINICAL TRIAL NUMBER: NCT05310721 IMPACT AND IMPLICATIONS: Time-restricted eating (TRE) is increasingly used for obesity management, but whether the timing of the eating window influences liver health remains unclear. In this 12-week multicenter randomized trial, adding early, late, or self-selected 8-hour TRE to Mediterranean diet-based usual care led to within-group reductions in MRI-assessed hepatic fat fraction, but did not confer greater improvements in hepatic fat fraction, liver health markers, or fecal microbiota than usual care alone. Participants with baseline metabolic dysfunction-associated steatotic liver disease (MASLD) and those achieving ≥5% weight loss experienced larger reductions in hepatic fat fraction, suggesting these reductions in this context are more closely linked to weight loss and baseline steatosis than to eating-window timing. Clinically, these findings support prioritizing feasible eating schedules and strategies that help patients attain clinically meaningful weight loss, particularly among individuals with MASLD.