Prolonged Overnight Fast on Energy Metabolism and Skeletal Muscle Protein Synthesis in Humans

The Effect of Prolonged Overnight Fast on Postprandial Energy Metabolism and Skeletal Muscle Protein Synthesis in Healthy Humans

Recent research shows that timing of nutritional intake and daily periods of fasting may have important health effects. In humans, limiting daily food intake to a narrow window (typically ~8 hours) can bring about some beneficial changes in blood concentrations of fats, sugar and the hormone insulin. It is thought that many of these changes are due to the prolonged daily fasting periods and humans will have regularly experienced prolonged fasting periods throughout evolution. In the modern era, food access is widely available and it is not uncommon for the time between breakfast and a late night snack to exceed 14 hours. We have recently shown that extending habitual daily periods of fasting to 16 hours per day also improves the ability of skeletal muscle to take up amino acids, the building blocks of protein. We are interested in studying whether a single episode of prolonged overnight fast (~16 hours), when compared to a normal overnight fast of 10 hours, is sufficient to stimulate skeletal muscle protein synthesis in response to dietary protein ingestion in healthy humans.

Study Overview

• Status: Recruiting
• Conditions: Time Restricted Feeding
• Intervention / Treatment: Other: Short 10hr fast; Other: Long 16h fast

Detailed Description

There is a growing interest in the cardiometabolic benefits of various intermittent fasting paradigms (such as alternate day fasting and the 5:2 fast diet), where periods of normal energy intake are punctuated by periods of energy restriction or fasting. A recent alternative to these protocols is time-restricted feeding (TRF), which limits daily food/energy intake to a narrow window (typically 8 to 10h). The major strength of TRF is that it extends the duration of overnight fast without limiting normal calorie intake. Recent evidence from both animal and human studies have shown that habitual daily periods of fasting of as little as 16h can reduce fasting insulin and triglycerides levels, protect against excessive body weight gain in response to high fat and sucrose diets, better maintain fat-free mass, and improve beta-cell responsiveness. We recently completed a 2-week TRF intervention study using the 8h fed (between 8am and 4pm)/16h fast protocol in healthy individuals and found improvements in insulin sensitivity and skeletal muscle uptake of branched chain amino acids. As we did not make measurements of muscle protein synthesis, it is not known whether a single episode of prolonged overnight fast (~16h) is sufficient to elicit improvements in insulin sensitivity and stimulate skeletal muscle protein synthesis in response to dietary protein ingestion. The aim of the proposed study is to investigate the effect of prolonged overnight fast (16h vs. 10h) on postprandial energy metabolism and skeletal muscle protein synthesis in healthy humans.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kostas Tsintzas, PhD; Phone Number: 0115 82 30127; Email: kostas.tsintzas@nottingham.ac.uk
• Study Contact Backup: Name: Joanne Mallinson, PhD; Phone Number: 01158219107; Email: joanne.mallinson@nottingham.ac.uk

Study Locations

• United Kingdom
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
      • Recruiting
      • University of Nottingham
      • Contact: Joanne Mallinson, PhD; Phone Number: 01158219107; Email: joanne.mallinson@nottingham.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male
• 18-35yrs
• healthy
• non-smoking
• physically active
• no excessive weight loss in past 6 months
• body mass index between 18 and 27 kg.m-2

Exclusion Criteria:

• body mass index under 18 and over 27 kg.m-2
• sedentary
• screening bloods out of range
• excessive weight loss in the past 6 months
• irregular eating patterns

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Short Fast; Participants will fast overnight for a period of 10 hours	Other: Short 10hr fast; Participants will fast from 11pm the night before the study day
Other: Long fast; Participants will fast overnight for a period of 16 hours	Other: Long 16h fast; Participants will fast from 5pm the night before the study day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity	Postprandial blood glucose and serum insulin concentrations will be measured every 15mins for 3 hours in response to ingestion of a protein and dextrose drink. Serum insulin concentration (mIU/l) will be measured either with an enzyme linked immunosorbent assay or a radioimmuno assay. Blood glucose will be measured using the glucose oxidase method.	3 hours
Skeletal muscle protein synthesis	Muscle protein synthesis will be measured 3 hours after ingestion of a protein and dextrose drink in which the milk protein has been intrinsically labelled with [1-13C]phenylalanine. We will measure [13C]phenylalanine incorporation into the muscle myofibrillar protein pool during the 3 hour period from a muscle biopsy sample taken pre ingestion of the drink and a muscle biopsy taken 3 hours post ingestion. This will give a rate (%/hour) of muscle protein synthesis.	3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal muscle insulin sensitivity	Postpandial arteriovenous differences in glucose concentration. Blood glucose in arteriliased and deep venous blood across the forearm will be measured using the glucose oxidase method.	3 hours

Collaborators and Investigators

• Sponsor: University of Nottingham

Publications and helpful links

General Publications

• Moro T, Tinsley G, Bianco A, Marcolin G, Pacelli QF, Battaglia G, Palma A, Gentil P, Neri M, Paoli A. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males. J Transl Med. 2016 Oct 13;14(1):290. doi: 10.1186/s12967-016-1044-0.
• Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CM. Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. Cell Metab. 2018 Jun 5;27(6):1212-1221.e3. doi: 10.1016/j.cmet.2018.04.010. Epub 2018 May 10.
• Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong EA, Gill S, Leblanc M, Chaix A, Joens M, Fitzpatrick JA, Ellisman MH, Panda S. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 2012 Jun 6;15(6):848-60. doi: 10.1016/j.cmet.2012.04.019. Epub 2012 May 17.
• Chaix A, Zarrinpar A, Miu P, Panda S. Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab. 2014 Dec 2;20(6):991-1005. doi: 10.1016/j.cmet.2014.11.001.
• Jones R, Pabla P, Mallinson J, Nixon A, Taylor T, Bennett A, Tsintzas K. Two weeks of early time-restricted feeding (eTRF) improves skeletal muscle insulin and anabolic sensitivity in healthy men. Am J Clin Nutr. 2020 Oct 1;112(4):1015-1028. doi: 10.1093/ajcn/nqaa192.

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2019
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: April 8, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 15, 2022

Study Record Updates

• Last Update Posted (Actual): June 15, 2022
• Last Update Submitted That Met QC Criteria: June 14, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: protein synthesis; skeletal muscle; Energy metabolism
• Other Study ID Numbers: 289-1904

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