Metabolic Effects of Late Dinner in Healthy Volunteers-A Randomized Crossover Clinical Trial

Abstract

Context: Consuming calories later in the day is associated with obesity and metabolic syndrome. We hypothesized that eating a late dinner alters substrate metabolism during sleep in a manner that promotes obesity.

Objective: The objective of this work is to examine the impact of late dinner on nocturnal metabolism in healthy volunteers.

Design and setting: This is a randomized crossover trial of late dinner (LD, 22:00) vs routine dinner (RD, 18:00), with a fixed sleep period (23:00-07:00) in a laboratory setting.

Participants: Participants comprised 20 healthy volunteers (10 male, 10 female), age 26.0 ± 0.6 years, body mass index 23.2 ± 0.7 kg/m2, accustomed to a bedtime between 22:00 and 01:00.

Interventions: An isocaloric macronutrient diet was administered on both visits. Dinner (35% daily kcal, 50% carbohydrate, 35% fat) with an oral lipid tracer ([2H31] palmitate, 15 mg/kg) was given at 18:00 with RD and 22:00 with LD.

Main outcome measures: Measurements included nocturnal and next-morning hourly plasma glucose, insulin, triglycerides, free fatty acids (FFAs), cortisol, dietary fatty acid oxidation, and overnight polysomnography.

Results: LD caused a 4-hour shift in the postprandial period, overlapping with the sleep phase. Independent of this shift, the postprandial period following LD was characterized by higher glucose, a triglyceride peak delay, and lower FFA and dietary fatty acid oxidation. LD did not affect sleep architecture, but increased plasma cortisol. These metabolic changes were most pronounced in habitual earlier sleepers determined by actigraphy monitoring.

Conclusion: LD induces nocturnal glucose intolerance, and reduces fatty acid oxidation and mobilization, particularly in earlier sleepers. These effects might promote obesity if they recur chronically.

Trial registration: ClinicalTrials.gov NCT03525717.

Keywords: late eating; cortisol; fatty acid oxidation; glucose; lipids; sleep.

© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Study procedures. Each participant underwent 2 clinical research unit (CRU) visits, 1 routine dinner (RD) visit and 1 late dinner (LD) visit, 3 to 4 weeks apart in random order. For each visit, participants were admitted for 2 consecutive nights, so that they had 1 night for acclimation to the CRU before undergoing procedures. Research breakfast, lunch, dinner, and snack were administered at specific times. H218O (0.4 g/kg) was given at 17:00 on both visits. [2H31] palmitate (15 mg/kg) was given mixed in a warm (60°C) liquid shake with dinner. Venous blood was sampled at times indicated by the arrows.

Figure 2.

In-lab activity. All values are reported as means ± SEM (n = 17). The hourly total activity counts (Fig. 2A) and active energy expenditure (Fig. 2B) are expressed as the total value in the subsequent hour from 08:00 on day 2 to 11:00 on day 3. Data for routine dinner and late dinner visits are shown in blue and red, respectively. The shaded region, from 23:00 to 07:00 denotes the sleep/lights-out period. The arrows denote dinner time, 18:00 for the routine dinner visit (blue) and 22:00 for the late dinner visit (red).

Figure 3.

Effect of late dinner on nocturnal and next-morning glucose and insulin levels. All values are reported as means ± SEM (n = 20). In Fig. 3A and 3C, data are plotted as a function of clock time at 1-hour intervals. In Fig. 3B and 3D, data are plotted as a function of time elapsed after dinner at 1-hour intervals. Data for the routine dinner and late dinner visits are shown in blue and red, respectively. The shaded region from 23:00 to 07:00 denotes the sleep/lights-out period. The arrows denote dinner time, 18:00 for the routine dinner visit (blue) and 22:00 for the late dinner visit (red). *Significant difference in values between 2 visits at denoted time points, analyzed by 2-sided paired t test (P < .05). #Significant difference in the 20-hour mean values between 2 visits, analyzed by 2-sided paired t test (P < .05).

Figure 4.

Effect of late dinner on nocturnal and next-morning triglycerides and free fatty acids levels. All values are reported as means ± SEM (n = 20). In Fig. 4A and 4C, data are plotted as a function of clock time at 1-hour intervals. In Fig. 4B and 4D, data are plotted as a function of time elapsed after dinner at 1-hour intervals. Routine dinner data are in blue; late dinner data are in red. The shaded region from 23:00 to 07:00 denotes the sleep/lights-out period. The arrows denote dinner time, 18:00 for the routine dinner visit (blue) and 22:00 for the late dinner visit (red). *Significant difference in values between 2 visits at denoted time points, analyzed by 2-sided paired t test (P < .05).

Figure 5.

Oral stable isotope data. All values are reported as means ± SEM (n = 17). In Fig. 5A, 5C, and 5E, data are plotted as a function of clock time at 1-hour intervals. In Fig. 5B, 5D, and 5F, data are plotted as a function of time elapsed after dinner at 1-hour intervals. Data for the routine dinner and late dinner visits are shown in blue and red, respectively. The shaded region from 23:00 to 07:00 denotes the sleep/lights-out period. The dashed arrows denote the time when H218O was consumed, 17:00 on both routine (blue) and late dinner (red) visits. The solid arrows denote dinner time, 18:00 for the routine dinner visit (blue) and 22:00 for the late dinner visit (red). *Significant difference in values between 2 visits at denoted time points, analyzed by 2-sided paired t test (P < .05).

Figure 6.

Effect of late dinner on nocturnal and next-morning cortisol levels. Values were plotted as means ± SEM as, Fig. 6A, a function of clock time or Fig. 6B, time elapsed after dinner at 1-hour intervals (n = 20). Routine dinner data are in blue; late dinner data are in red. The shaded region from 23:00 to 07:00 denotes the sleep/lights-out period. The arrows denote dinner time, 18:00 for the routine dinner visit (blue) and 22:00 for the late dinner visit (red). *Significant difference in values between 2 visits at denoted time points, analyzed by 2-sided paired t test (P < .05). #Significant difference in the 20-hour mean values between 2 visits, analyzed by 2-sided paired t test (P < .05).

Figure 7.

Associations between metabolic responses to late dinner and habitual sleep onset. A, Scatter plot matrix between percentage increase in 4-hour postdinner glucose area under the curve (AUC) (LD – RD), change in FAO rate (LD – RD), and habitual sleep onset. B, Scatter plot and linear regression line with 95% confidence bands predicting percentage increase in 4-hour postdinner glucose AUC (LD – RD) as a function of habitual sleep onset. C, Scatter plot and linear regression line with 95% confidence bands predicting change in FAO rate (LD – RD) as a function of habitual sleep onset. Habitual sleep onset is the average of the 2 preadmission mean sleep onset measurements by actigraphy, expressed as hour post-MN. AUC, area under the curve; FAO rate, cumulative fatty acid oxidation at 14 hours after dinner divided by 14 hours; LD, late dinner; MN, midnight; RD, routine dinner.