Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes

Abstract

Intermittent fasting (IF) improves cardiometabolic health; however, it is unknown whether these effects are due solely to weight loss. We conducted the first supervised controlled feeding trial to test whether IF has benefits independent of weight loss by feeding participants enough food to maintain their weight. Our proof-of-concept study also constitutes the first trial of early time-restricted feeding (eTRF), a form of IF that involves eating early in the day to be in alignment with circadian rhythms in metabolism. Men with prediabetes were randomized to eTRF (6-hr feeding period, with dinner before 3 p.m.) or a control schedule (12-hr feeding period) for 5 weeks and later crossed over to the other schedule. eTRF improved insulin sensitivity, β cell responsiveness, blood pressure, oxidative stress, and appetite. We demonstrate for the first time in humans that eTRF improves some aspects of cardiometabolic health and that IF's effects are not solely due to weight loss.

Keywords: blood pressure; circadian rhythms; circadian system; eTRF; early time-restricted feeding; insulin resistance; insulin sensitivity; intermittent fasting; meal timing; prediabetes.

Conflict of interest statement

DECLARATION OF INTERESTS

The authors declare no competing interests.

Copyright © 2018 Elsevier Inc. All rights reserved.

Figures

Figure 1. Dietary Interventions

(A) Meal Timing Interventions. An example schedule for a person who eats breakfast at 07:00 h. (B) Study Menus. Food was prepared according to a five-day sequence of menus. Each menu provided three meals/day and was composed of 35% fat, 50% carbohydrate, and 15% protein. Caloric intake was tailored to each participant’s unique energy requirements, and each meal provided about 33% of daily caloric needs. See alsoFigure S1 and Table S1.

Figure 2. Glycemic Control

eTRF did not affect (A) individual or (B) mean values for glucose during a 3-hour OGTT. However, eTRF did lower (C) insulin levels at multiple time points and (D) mean insulin levels. Overall, eTRF improved (E) β cell responsiveness and (F) insulin resistance, as measured by the insulinogenic index and the incremental AUC ratio, respectively. (Post-intervention values shown above for (A) glucose and (C) insulin were adjusted for differences at baseline.) All data are paired, with N=8 completers in each arm. Data are presented as least squares mean ± SEM, with the exceptions of panels A and C, which display the data as raw mean ± SEM. * p ≤ 0.05. See alsoFigure S2 and Table S2.

Figure 3. Cardiovascular Disease Risk Factors

eTRF dramatically lowered (A) systolic blood pressure and (B) diastolic blood pressure in the morning. However, it increased or tended to increase morning values for (E) resting heart rate, (I) triglycerides, and, in turn, (F) total cholesterol. The (C) augmentation index, (D) pulse wave velocity, (G) LDL cholesterol, and (H) HDL cholesterol were unaffected. All data are paired, with N=8 completers in each arm. Data are presented as least squares mean ± SEM. * p ≤ 0.05. See alsoTable S2.

Figure 4. Inflammatory and Oxidative Stress Markers

eTRF did not affect the inflammatory markers (A) hs-CRP, (B) IL-6, or (C) cortisol. However, eTRF reduced levels of (D) 8-isoprostane, a marker of oxidative stress to lipids. All data are paired, with N=8 completers in each arm. Data are presented as least squares mean ± SEM. * p ≤ 0.05. See alsoTable S2.

Figure 5. Subjective Appetite

Participants rated their appetite on a 0–100 mm visual analog scale, ranging from “Not at All” (0 mm) to “Extremely” (100 mm). (A–E) eTRF did not affect appetite in the morning. In the evening, eTRF reduced (A) desire to eat and (B) capacity to eat and increased (D) feelings of fullness. Changes in evening levels of (C) hunger and (E) stomach fullness did not quite reach statistical significance. All data are paired, with N=8 completers in each arm. Data are presented as least squares mean ± SEM. * p ≤ 0.05. See alsoTable S2 and Figure S3.