Physiological and Sensory Responses to Prolonged Fasting in Humans (PRO-FAST)

This study aims to establish the metabolic/molecular response in both adipose tissue and skeletal muscle as well as sensory experiences (pain, fatigue, drive) to prolonged fasting of 3 days duration. Participants will undergo sequential meal assessment before and after a 3 day fast with measures taken throughout each fasting day.

Study Overview

• Status: Active, not recruiting
• Conditions: Adiposity; Metabolic Disturbance; Fasting; Energy Supply; Deficiency
• Intervention / Treatment: Other: Prolonged Fasting

Detailed Description

This study will employ a single-arm, non-randomised design in which participants will act as their own control prior to undergoing 3 days of fasting. The control phase includes 3 days of habitual energy balance assessment before coming into the laboratory for baseline meal testing with blood, muscle, and adipose samples as well as anthropometric assessment.

Participants will then be provided with a standardised lunch to be consumed around midday and a standardised dinner to be consumed at 2000 h.

Participants will then be asked to refrain from caloric intake for 3 days until they return to the laboratory for follow up measures.

Participants will be provided with monitoring equipment throughout the 3 days of fasting and will be asked to provide a blood sample at 0800 h each day alongside self recording of blood pressure, weight, and urinary ketones each day. On the middle day (day 2) participants will also be asked to come into the lab to provide a blood sample at 2000 h.

The follow up visit will be identical to that performed before the fast, including meal testing, blood, muscle, and adipose samples.

• Study Type: Interventional
• Enrollment (Estimated): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Somerset
    • Bath, Somerset, United Kingdom, BA2 7AY
      • University of Bath

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• • Body mass index 20.0-29.9 kg∙m-2

  • Age 18-45 years
  • Willing to abstain from food intake for just over 3 days (~82 hours)
  • Able and willing to provide informed consent and safely comply with study procedures
  • Females to maintain record of regular menstrual cycle phase or contraceptive use
  • No anticipated changes in lifestyle during the study (e.g. holidays or exercise programmes)

Exclusion Criteria:

• • Any reported condition or behaviour deemed either to pose undue personal risk to the participant or introduce bias

  • Any diagnosed metabolic disease (e.g. type 1 or type 2 diabetes)
  • Any reported use of substances which may pose undue personal risk to the participants or introduce bias into the experiment
  • Pregnancy
  • Breastfeeding
  • Lifestyle not conforming to standard sleep-wake cycle (e.g. shift worker)
  • History of eating disorders (e.g. anorexia)
  • Any reported recent (<6 months) change in body mass (± 3%)
  • Uncontrolled hyperthyroidism
  • Advanced cerebrovascular insufficiency or dementia
  • Advanced liver or kidney insufficiency
  • History of migraine and or headache
  • Psychotic disorders
  • Unstable or severe coronary artery disease
  • Retinal detachment
  • Duodenal or stomach ulcer
  • Cancer and malignant disease
  • Regular use of Non-steroidal anti-inflammatory drugs (NSAIDs)
  • Use of Systemic corticoids
  • Use of Antihypertensives (especially beta-blockers and diuretics)
  • Use of Antidiabetics
  • Use of Anti-coagulants
  • Use of Psychotropics (especially neuroleptics and lithium)
  • Use of Anticonvulsants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prolonged Fasting; All participants are asked to act as their own control prior to being asked to undergo 3 days of fasting.	Other: Prolonged Fasting; Participants are asked to refrain from caloric intake for 3 days following a period of habitual lifestyle assessment and metabolic assessment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in postprandial insulin responses	Change in postprandial insulin (mmol/L) response to a standardised meal before and after 3 days of fasting.	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in circulating glycerol and non-esterified fatty acids	Change in indices of lipolysis from adipose tissue in response to prolonged fasting (Glycerol mmol/L; NEFA mmol/L)	1 day, 2 days, 3 days
Change in Autophagy	Change in autophagic flux in response to prolonged fasting, assessed in skeletal muscle and circulating neutrophils.	3 days
Change in plasma lactate	Change in plasma lactate in response to prolonged fasting (indices of Cori cycle)	1 day, 2 days, 3 days
Change in plasma pyruvate	Change in plasma pyruvate in response to prolonged fasting (indices of Cori cycle)	1 day, 2 days, 3 days
Change in ketosis.	Change in urinary (acetoacetate) ketones in response to prolonged fasting.	1 day, 2 days, 3 days.
Change in ketosis.	Change in circulating (beta-hydroxybutyrate) ketones in response to prolonged fasting.	1 day, 2 days, 3 days.
Change in body mass	Change in body mass, pre-post, and during the prolonged fast.	1 day, 2 days, 3 days.
Change in blood pressure	Change in blood pressure pre-, post-, and during the prolonged fast	1 day, 2 days, 3 days.
Change in interstitial fluid glucose concentrations	Change in interstitial fluid glucose concentrations pre-, post-, and during the prolonged fast (assessed via continual glucose monitoring)	1 day, 2 days, 3 days.
Change in amino acid metabolism	Change in amino acid metabolism (i.e. BCAAs and ketoacids) in skeletal muscle	3 days.
Change in amino acid metabolism	Change in amino acid metabolism (i.e. BCAAs and ketoacids) in adipose tissue	3 days.
Change in amino acid metabolism	Change in amino acid metabolism (i.e. BCAAs and ketoacids) in circulation	3 days.
Change in postprandial glucose responses.	Change in postprandial glucose (mmol/L) response to a standardised meal before and after 3 days of fasting.	3 days.

Collaborators and Investigators

• Sponsor: University of Bath
• Collaborators: University of Nottingham

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2021
• Primary Completion (Estimated): May 30, 2024
• Study Completion (Estimated): May 30, 2024

Study Registration Dates

• First Submitted: September 7, 2021
• First Submitted That Met QC Criteria: July 26, 2023
• First Posted (Actual): August 4, 2023

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: July 26, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: PF

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