Effects of Time-Restricted Eating on Ketone Metabolism and Immunoregulation in Premenopausal Women: Protocol for a Pilot, Prospective, Single-Arm Dietary Intervention Study

BACKGROUND: Intermittent fasting interventions, such as time-restricted eating (TRE) without calorie restriction, may offer diverse cardiometabolic health benefits, including reductions in inflammation. However, the underlying metabolic mechanisms are poorly understood. OBJECTIVE: This study is designed to evaluate ketone metabolism and immunoregulation during TRE (6-hour feeding and 18-hour fasting) without caloric restriction compared to a conventional dietary regimen (12-hour feeding and 12-hour fasting) in women. METHODS: This is a pilot, prospective, single-arm dietary intervention study in premenopausal women classified as lean and obese, with intraindividual and stratified comparisons. Ketone turnover, immunologic responses, and metabolic profiles will be compared between a conventional dietary regimen (12-hour feeding and 12-hour fasting) at admission and after 3 days of TRE (6-hour feeding and 18-hour fasting). RESULTS: The trial commenced in August 2024. As of February 2026, participant enrollment is ongoing. Complete enrollment is expected in the December 2026. Integrated analyses will be reported once data analysis is completed, which is expected in the winter of 2027. CONCLUSIONS: This clinical protocol will evaluate whole-body ketone metabolism and immunoregulatory changes in women during TRE using state-of-the-art stable isotope and immunophenotyping techniques. This study will determine the effects of a time-limited dietary pattern, without caloric restriction, on dynamic measures of immunity and metabolism. TRIAL REGISTRATION: ClinicalTrials.gov NCT06169137; https://clinicaltrials.gov/study/NCT06169137. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/81063.