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.
Highlights
Intermittent fasting (IF) covers a broad class of interventions that alternate periods of eating and extended fasting
In our first 5-week crossover study, we found that early time-restricted feeding (eTRF) reduces insulin levels, improves insulin sensitivity, lowers blood pressure, and decreases lipid peroxidation in men with prediabetes [18]
We investigated the effects of meal timing on selected hormones that are thought to be responsive to and/or mediate the beneficial effects of fasting (Figure 5). eTRF did not affect any of the hormones in the morning (p ≥ 0.26), except cortisol, which tended to increase by 1.5 ± 0.9 μg/dl (p = 0.10)
Summary
Intermittent fasting (IF) covers a broad class of interventions that alternate periods of eating and extended fasting. IF interventions include periodic 24-hour fasts, intermittent energy restriction (e.g., the 5:2 diet), and time-restricted feeding. Data on IF is limited but suggest that it decreases body weight, insulin levels, blood pressure, inflammation, and appetite, and that it improves insulin sensitivity and lipid profiles [1,3,4,5]. These clinical benefits are driven by a reduction in insulin levels; improved insulin signaling; a reduction in oxidative stress; an increase in antioxidant defenses. Since the median American eats over a 12-hour period [20], we define TRF as eating within a ≤10-hour period and fasting for at least 14 hours per day
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