Clinical trial NCT05420181: Prolonged Overnight Fast, Energy Metabolism and Skeletal Muscle Anabolic Sensitivity
Official title: The Effect of Prolonged Overnight Fast on Postprandial Energy Metabolism and Skeletal Muscle Anabolic Sensitivity in Healthy Humans
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Time Restricted Feeding
Keywords: Energy metabolism
skeletal muscle
protein synthesis
Lead sponsor: University of Nottingham
Sponsor class: OTHER
First posted: 2022-06-15
Enrollment: 9
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Whole body Insulin sensitivity
timeFrame: 3 hours
measure: Glycemic responses
timeFrame: 3 hours
measure: Insulinaemic responses
timeFrame: 3 hours
measure: Index of skeletal muscle protein synthesis (A)
timeFrame: 3 hours
measure: Index of skeletal muscle protein synthesis (B)
timeFrame: 3 hours
Secondary outcomes:
measure: Skeletal muscle insulin sensitivity
timeFrame: 3 hours
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: University of Nottingham
state: Nottinghamshire
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.