Effects of Time-restricted Eating on Nutrient Absorption in Healthy Adults

This 2-period, crossover, controlled-feeding trial will investigate the effects of early time-restricted eating (8am-2pm), compared to a control eating timeframe (8am-8pm), on energy and macronutrient digestibility, the thermic effect of food (TEF), postprandial blood metabolites, 24 h glucose concentrations, glycemic variability, intestinal hydrogen gas production, gastrointestinal transit time, and microbiome composition. This study will also seek to determine factors that may predict intestinal absorption efficiency (i.e., digestibility) including the microbial composition of stool, fasting and postprandial metabolomics, gastrointestinal transit time, thermic effect of food, 24 h glucose concentrations and variability, and hydrogen gas production.

Study Overview

• Status: Completed
• Conditions: Digestibility
• Intervention / Treatment: Other: weight maintenance diet (WMD)

Detailed Description

The obesity epidemic is well documented, and despite a complex etiology influenced by genetic, physiological, psychological, social, behavioral, and environmental factors, obesity seems to be the result of energy imbalance, where energy intake exceeds energy expenditure, regardless of the internal and external influences. Studies aiming to quantify and manipulate modulators of energy balance, including gastrointestinal (GI) energy absorption rates (i.e., digestibility), are crucial for reducing the incidence of overweight and obesity and improving overall human health. Despite considerable interindividual variability in the amount of ingested energy that is absorbed (~87-98% of ingested energy) by the gastrointestinal tract, generalized equations are used to calculate individual energy intake requirements, and the factors that contribute to such variability, including meal-timing, are largely unknown.

The proposed study seeks to determine the effects of restricting the eating window to 6-h (early time-restricted eating) as compared to a control eating window of 12 h on energy and macronutrient digestibility, thermic effect of food (TEF), postprandial blood metabolites (triglyceride, insulin, glucose, fructose, galactose, inositol, and sorbitol), 24 h glucose concentrations and glycemic variability, intestinal hydrogen gas production, microbiome composition, and gastrointestinal transit time in response to a controlled, energy balanced diet. In addition, this project will determine whether energy digestibility can be predicted from biological and physiological factors such as gut microbiota composition, gastrointestinal transit time, 24-h glucose concentrations, and postabsorptive and postprandial metabolomic profiles.

Participants will be randomized to early TRE (6-h feeding window, 8am-2pm) or a control eating schedule (12-h feeding window, 8am-8pm) and consume a controlled, energy balance diet (breakfast, lunch, dinner, snacks, and beverages) for 9 consecutive days before crossing over to the other intervention after at least a 3-wk washout for females (to control for hormonal fluctuations) and at least a 2-wk washout for males. Participants will collect stool and urine during each feeding phase. Gross energy content (heat combustion by bomb calorimetry) of the diet, stool, and urine samples will be used to calculate energy digestibility (diet gross energy - stool gross energy) and metabolizable energy. Factors that may mediate and/or predict energy digestibility efficiency, including gastrointestinal microbial composition, transit time, and gas production, fasting and postprandial metabolites, continuous glucose concentrations, and thermogenesis will be assessed.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tallahassee, Florida, United States, 32306
      • Florida State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 20-45 years old
• Normal weight or overweight (18.5 to 29.9 kg/m2)
• Not taking any probiotics for 4 weeks prior to and throughout the entire study
• Willing to refrain from smoking, vaping, chewing tobacco, and dietary supplement use throughout the study
• Willing to consume a controlled diet for 9 consecutive days on 2 different occasions (18 days total) and collect all urine and fecal output for 3-5 days during each occasion
• Pass the blue dye gastrointestinal tracer (given at screening) within 72 hours of administration

Exclusion Criteria:

• Metabolic or cardiovascular abnormalities, gastrointestinal disorders, prior bariatric surgery, malabsorption, or any condition that interferes with metabolism (e.g., kidney disease, diabetes, cardiovascular disease, etc.)
• Suspected or known strictures, fistulas, or physiological/mechanical gastrointestinal obstruction
• Present condition of alcoholism, anabolic steroids, or other substance abuse issues
• Women who are pregnant, lactating, planning to become pregnant, or who have an irregular menstrual cycle in the past 6 months
• Weight fluctuations ± 5% of body weight in the last 6 months
• Allergies or intolerance to foods included in the controlled diet
• Any use of antibiotics, except topical antibiotics, within 3 months of study participation
• Colonoscopy within 3 months of study participation
• Use of laxatives, stool softeners, or anti-diarrheal medications more than once a week within 4-weeks of study enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: early time-restricted eating (eTRE); Participants will be provided a weight-maintenance diet for 9 consecutive days and will consume all meals and snacks in a 6-h window in the morning hours (e.g., 8:00 AM - 2:00 PM)	Other: weight maintenance diet (WMD); A diet meeting the participant's weight maintenance energy needs will be provided.
Experimental: control eating schedule (CON); Participants will be provided a weight-maintenance diet for 9 consecutive days and will consume all meals and snacks in a 12-h window in the morning hours (e.g., 8:00 AM - 8:00 PM)	Other: weight maintenance diet (WMD); A diet meeting the participant's weight maintenance energy needs will be provided.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Energy digestibility	Calculated as gross energy of the diet (kcals) - gross energy excreted in stool (kcals)	Days 4-9

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fat digestibility	Calculated as fat content of the diet - fat content excreted in stool	Days 4-9
Carbohydrate digestibility	Calculated as carbohydrate content of the diet - carbohydrate content excreted in stool	Days 4-9
Protein digestibility	Calculated as protein content of the diet - protein content excreted in stool	Days 4-9
Metabolizable energy	Calculated as gross energy of the diet (kcals) - gross energy excreted in urine and stool (kcals)	Days 4-9
Metabolizable protein	Calculated as protein content of the diet - protein excreted in urine and stool	Days 4-9
Postabsorptive and postprandial plasma metabolites	Plasma metabolites will be measured using gas chromatography coupled with mass spectrometry in the postabsorptive state and following a standardized meal (1 hour, 2 hours, 3 hours, and 4 hours after meal intake).	Day 6
Gut microbiome	Microbiota composition and diversity will be determined using 16S rRNA gene sequencing.	Day 6
Gastrointestinal transit time	A gas-sensing capsule will be ingested to measure transit time in the gastrointestinal tract.	Day 6
Gastrointestinal gas production	A gas-sensing capsule will be ingested to measure hydrogen, carbon dioxide, and oxygen production in the gastrointestinal tract.	Day 6
Gastrointestinal temperature	A gas-sensing capsule will be ingested to measure temperature in the gastrointestinal tract.	Day 6
24-h glucose concentrations	A continuous glucose monitor will be used to collect and assess 24-h glucose concentrations.	Days 1-8
24-h glucose variability	A continuous glucose monitor will be used to collect and assess 24-h glucose variability.	Days 1-8
Thermic effect of food	Indirect calorimetry measures will be collected in the resting state and for 4 hours (15-30, 45-60, 75-90, 105-120, 165-180, and 225-240 minutes) following the consumption of a standardized meal.	Day 6

Collaborators and Investigators

• Sponsor: Florida State University
• Investigators: Principal Investigator: Claire E Berryman, Ph.D., Florida State University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Actual): June 10, 2022
• Study Completion (Actual): June 10, 2022

Study Registration Dates

• First Submitted: March 14, 2021
• First Submitted That Met QC Criteria: May 3, 2021
• First Posted (Actual): May 7, 2021

Study Record Updates

• Last Update Posted (Actual): June 23, 2022
• Last Update Submitted That Met QC Criteria: June 22, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: overweight; microbiome; metabolomics; energy balance; digestibility; intestinal absorption; stool energy loss
• Other Study ID Numbers: STUDY00001564

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No