Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans

TLDR

Time‑restricted feeding (TRF) is a form of intermittent fasting that extends the daily fasting period and has been shown in preliminary studies to improve cardiometabolic health in rodents and humans. This study aimed to determine how TRF influences gene expression, circulating hormones, and diurnal patterns of cardiometabolic risk factors in humans. Eleven overweight adults completed a 4‑day randomized crossover trial comparing early TRF (8 am–2 pm) with a control schedule (8 am–8 pm), during which continuous glucose monitoring and blood sampling assessed cardiometabolic risk factors, hormones, and whole‑blood gene expression. Early TRF lowered mean 24‑hour glucose by 4 mg/dl, reduced glycemic excursions, increased ketones, cholesterol, SIRT1, LC3A, and MTOR expression, altered cortisol and circadian clock gene rhythms, and overall improved glucose control, lipid metabolism, and markers of autophagy and anti‑aging in humans.

Abstract

Time-restricted feeding (TRF) is a form of intermittent fasting that involves having a longer daily fasting period. Preliminary studies report that TRF improves cardiometabolic health in rodents and humans. Here, we performed the first study to determine how TRF affects gene expression, circulating hormones, and diurnal patterns in cardiometabolic risk factors in humans. Eleven overweight adults participated in a 4-day randomized crossover study where they ate between 8 am and 2 pm (early TRF (eTRF)) and between 8 am and 8 pm (control schedule). Participants underwent continuous glucose monitoring, and blood was drawn to assess cardiometabolic risk factors, hormones, and gene expression in whole blood cells. Relative to the control schedule, eTRF decreased mean 24-hour glucose levels by 4 ± 1 mg/dl (p = 0.0003) and glycemic excursions by 12 ± 3 mg/dl (p = 0.001). In the morning before breakfast, eTRF increased ketones, cholesterol, and the expression of the stress response and aging gene SIRT1 and the autophagy gene LC3A (all p < 0.04), while in the evening, it tended to increase brain-derived neurotropic factor (BNDF; p = 0.10) and also increased the expression of MTOR (p = 0.007), a major nutrient-sensing protein that regulates cell growth. eTRF also altered the diurnal patterns in cortisol and the expression of several circadian clock genes (p < 0.05). eTRF improves 24-hour glucose levels, alters lipid metabolism and circadian clock gene expression, and may also increase autophagy and have anti-aging effects in humans.