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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Time Restricted Feeding

Intervention / Treatment
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* Other: Short 10hr fast
* Other: Long 16h fast


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Energy metabolism, skeletal muscle, protein synthesis