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

“Diet and Exercise Will Help You Live Longer”: The Meme that Turns on Housekeeping Genes

“…Advances in Geriatric Medicine and Research 18 of 32 the macronutrient to restrict during CR or IF in order to promote fatty acid and ketone oxidation. However, in the studies discussed in this paper, carbohydrate intake was between that of a normal Western diet, ~45-60% of daily energy intake, during CR and IF periods [22,166,167,169,185,[194][195][196]. Daily protein intake, on the other hand, was kept under ~15% of daily kcals.…”

“…Alternatively, IF involves frequent, short-duration CR such as "5:2 fasting", alternate day fasting, periodic fasting, and daily TRF, all which are capable of producing health benefits comparable to that of CR [183][184][185]. The 5:2 fasting protocol involves ad libitum feeding 5-days per week with 2-days of severe CR (i.e., 500 kcals/day) or complete cessation of caloric intake (i.e., 24-h fast) on non-consecutive days [179,183].…”

“…Insulin can also activate Akt-PI3K growth factor signaling [203] and inhibit autophagy [204]. However, as demonstrated by the cited studies, amid CR and IF, carbohydrate intake and subsequent insulin signaling does not impair their longevity promoting effects or autophagy activity [22,166,167,169,185,[194][195][196].…”

Recent Evidence on the Impact of Ramadan Diurnal Intermittent Fasting, Mealtime, and Circadian Rhythm on Cardiometabolic Risk: A Review

“…The study demonstrated that early TRF (6-h feeding period, with dinner before 3 p.m.) led to reduced blood pressure, oxidative stress, and appetite, and increased insulin sensitivity and β cell responsiveness compared to the controls (12-h feeding period) for 5 weeks (28). Another two recent studies assessed the effect of early TRF (08:00-14:00) vs. a control protocol (08:00-20:00) in a randomized crossover design on 11 overweight adults (28,29). Early TRF significantly reduced the mean 24-h glucose levels and glycemic excursions (29).…”

“…Another two recent studies assessed the effect of early TRF (08:00-14:00) vs. a control protocol (08:00-20:00) in a randomized crossover design on 11 overweight adults (28,29). Early TRF significantly reduced the mean 24-h glucose levels and glycemic excursions (29). Moreover, the early time-feeding protocol led to decreased appetite without affecting energy expenditure (30).…”