Impacts of Intermittent Fasting in Adults on Energy Balance, Body Composition, Postprandial Hormone Profiles and Gene Expression in Adipose Tissue
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Bath
- Enrollment
- 54
- Locations
- 1
- Primary Endpoint
- FASN Gene Expression in Subcutaneous Adipose Tissue
Study Overview
Brief Summary
Obesity is a global concern with links to conditions such as diabetes. Historically, these conditions have been managed by reducing energy intake on a daily basis, which is often hampered by low adherence rates and compensatory reductions in physical activity. Intermittent fasting (IMF) has become popular as an alternative method of weight loss, where periods of normal eating are punctuated by days of fasting. However, despite its popularity, IMF is scarcely examined within the literature.
This study will examine the impact of IMF on energy balance and the associated health outcomes relating to conditions such as diabetes. To achieve this, 36 lean adults and 36 overweight/obese adults will be recruited, excluding those with conditions which may be adversely affected by fasting. Once enrolled, participants will complete a one month control phase, incorporating 12 days of diet and activity monitoring, to ensure their weight is stable before moving in to the intervention phase.
The intervention phase will begin with a lab protocol designed to examine body composition, resting metabolic rate and metabolic responses to two successive meals. Once completed, participants will be randomised to one of three diets which are listed below. Comparing the changes seen with diets 1 and 2 will provide the first direct comparison of IMF against more conventional strategies, while diet 3 will allow us to ascertain the role of weight loss in mediating any effects of IMF.
- Daily calorie restriction - Reduce energy intake by 25% on a daily basis
- IMF with weight loss - Alternate between 24 hour cycles of fasting and feeding with 150% of normal intake when feeding
- IMF without weight loss - Alternate between 24 hour cycles of fasting and feeding with 200% of normal intake when feeding
All three diets will last for 20 consecutive days, with transitions between each 24 hour diet cycle occurring at 15:00 each day to allow at least one main meal per day. When fasting, participants will only be permitted water and black tea/coffee to eliminate energy intake. Once again physical activity and diet will be monitored for 12 days during the intervention to examine changes in energy expenditure and ensure compliance.
Having completed all 20 diet cycles participants will return to the laboratory to repeat the protocol described earlier. Comparing these results against the values seen before the intervention will then allow the effects of IMF to be identified and compared.
Detailed Description
Recruitment
Local advertising in the form of posters will distributed throughout the research institution, nearby organisations and the city of Bath. The posters will encourage interested persons to contact the chief investigator to receive more information on what the study will involve. The research team will be looking to recruit 72 (36 lean, 36 overweight/obese) individuals who satisfy the entry criteria (discussed later).
Enrolment
Potential volunteers will use the contact details provided in advertising materials to express their interest to the research team who will then provide them with a copy of the participant information sheet to read through at their convenience. Those interested in participating will then be invited to a pre-enrolment consultation where they will be given the opportunity to ask any questions they may have about the study before being screened for the inclusion and exclusion criteria. This will involve measurements of weight and height, as well as the completion of an entry criteria questionnaire, the Eating Disorder Examination Questionnaire and the Physical Activity Readiness Questionnaire. Providing they satisfy the relevant criteria they will be talked through the study and before being asked to complete an informed consent form. As part of this, the procedure for an adipose tissue biopsy will be discussed with the participant and they will be asked to decide whether or not they would like to include this as it is an optional test.
Baseline Lab Protocol (LAB 1)
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Body Mass Index of 20.5 kg/m2 or greater
- •Stable body weight for preceding three months (<3 kg increase or decrease)
- •Able and willing to safely comply with study procedures
- •Be able to attend the laboratory and willing to participate in necessary protocols
- •Be willing to undertake the durations of fasting required by the study
- •Have the capacity and willingness to provide informed consent (oral and written)
Exclusion Criteria
- •Have a body weight greater than 120 kg
- •Will be undertaking any other fasting practices during their participation in the study (can enrol once stable weight returns after fasting is completed)
- •Currently engaged in or planning to engage in another weight management programme (e.g. weight watchers) or exercise programme (e.g. hypertrophy training or marathon training) during the study
- •Have previously suffered or are suffering from an eating disorder as assessed using the Eating Disorder Examination Questionnaire, Version 6.0 (Fairburn & Beglin, 2008)
- •Have been diagnosed with either type 1 or type 2 diabetes
- •Undertaking any form of medical treatment which may interfere with study variables (e.g. chemotherapy, liposuction, taking metformin, statins/other lipid-lowering medications)
- •Are peri-menopausal or menopausal (absence of menses for 3-24 months)
- •Pregnant, recently pregnant (within last 6 months), planning to become pregnant (within next six months), or currently breastfeeding.
- •Have donated more than 500 ml of blood in the last three months before the initial laboratory visit
- •Lack of metal capacity or language skills to independently understand/follow the study protocol
- •Physical disability which impacts study variables or ability to independently follow study protocol (e.g. paralysis)
- •Cannot consume test meals due to intolerances (i.e. lactose)
- •Report medical contraindications on the 'Physical Activity Readiness Questionnaire' and are unable to obtain medical approval for the treadmill test.
Arms & Interventions
Daily Calorie Restriction (DCR)
During the intervention phase, participants randomised to this treatment condition will be asked to reduce their normal energy intake by 25% on a daily basis.
Intervention: Physical Activity Monitoring (Actiheart) (Device)
Daily Calorie Restriction (DCR)
During the intervention phase, participants randomised to this treatment condition will be asked to reduce their normal energy intake by 25% on a daily basis.
Intervention: Energy Intake Monitoring (Other)
Daily Calorie Restriction (DCR)
During the intervention phase, participants randomised to this treatment condition will be asked to reduce their normal energy intake by 25% on a daily basis.
Intervention: Body Weight Monitoring (Other)
Daily Calorie Restriction (DCR)
During the intervention phase, participants randomised to this treatment condition will be asked to reduce their normal energy intake by 25% on a daily basis.
Intervention: Intravenous Cannulation (Procedure)
Daily Calorie Restriction (DCR)
During the intervention phase, participants randomised to this treatment condition will be asked to reduce their normal energy intake by 25% on a daily basis.
Intervention: Adipose Tissue Biopsy (Procedure)
Daily Calorie Restriction (DCR)
During the intervention phase, participants randomised to this treatment condition will be asked to reduce their normal energy intake by 25% on a daily basis.
Intervention: Lidocaine Hydrochloride (Drug)
Daily Calorie Restriction (DCR)
During the intervention phase, participants randomised to this treatment condition will be asked to reduce their normal energy intake by 25% on a daily basis.
Intervention: Post-Prandial Meal Tests (Other)
Daily Calorie Restriction (DCR)
During the intervention phase, participants randomised to this treatment condition will be asked to reduce their normal energy intake by 25% on a daily basis.
Intervention: DEXA Scan (Radiation)
Daily Calorie Restriction (DCR)
During the intervention phase, participants randomised to this treatment condition will be asked to reduce their normal energy intake by 25% on a daily basis.
Intervention: Actiheart Calibration (Other)
Daily Calorie Restriction (DCR)
During the intervention phase, participants randomised to this treatment condition will be asked to reduce their normal energy intake by 25% on a daily basis.
Intervention: Daily Calorie Restriction (Other)
Fasting with Weight Loss (IMF-WL)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 150% of normal energy intake) and fasting (no energy intake).
Intervention: Physical Activity Monitoring (Actiheart) (Device)
Fasting with Weight Loss (IMF-WL)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 150% of normal energy intake) and fasting (no energy intake).
Intervention: Energy Intake Monitoring (Other)
Fasting with Weight Loss (IMF-WL)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 150% of normal energy intake) and fasting (no energy intake).
Intervention: Body Weight Monitoring (Other)
Fasting with Weight Loss (IMF-WL)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 150% of normal energy intake) and fasting (no energy intake).
Intervention: Intravenous Cannulation (Procedure)
Fasting with Weight Loss (IMF-WL)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 150% of normal energy intake) and fasting (no energy intake).
Intervention: Adipose Tissue Biopsy (Procedure)
Fasting with Weight Loss (IMF-WL)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 150% of normal energy intake) and fasting (no energy intake).
Intervention: Lidocaine Hydrochloride (Drug)
Fasting with Weight Loss (IMF-WL)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 150% of normal energy intake) and fasting (no energy intake).
Intervention: Post-Prandial Meal Tests (Other)
Fasting with Weight Loss (IMF-WL)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 150% of normal energy intake) and fasting (no energy intake).
Intervention: DEXA Scan (Radiation)
Fasting with Weight Loss (IMF-WL)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 150% of normal energy intake) and fasting (no energy intake).
Intervention: Actiheart Calibration (Other)
Fasting with Weight Loss (IMF-WL)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 150% of normal energy intake) and fasting (no energy intake).
Intervention: Intermittent Fasting with Weight Loss (Other)
Fasting without Weight Loss (IMF-WS)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 200% of normal energy intake) and fasting (no energy intake).
Intervention: Physical Activity Monitoring (Actiheart) (Device)
Fasting without Weight Loss (IMF-WS)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 200% of normal energy intake) and fasting (no energy intake).
Intervention: Energy Intake Monitoring (Other)
Fasting without Weight Loss (IMF-WS)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 200% of normal energy intake) and fasting (no energy intake).
Intervention: Body Weight Monitoring (Other)
Fasting without Weight Loss (IMF-WS)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 200% of normal energy intake) and fasting (no energy intake).
Intervention: Intravenous Cannulation (Procedure)
Fasting without Weight Loss (IMF-WS)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 200% of normal energy intake) and fasting (no energy intake).
Intervention: Adipose Tissue Biopsy (Procedure)
Fasting without Weight Loss (IMF-WS)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 200% of normal energy intake) and fasting (no energy intake).
Intervention: Lidocaine Hydrochloride (Drug)
Fasting without Weight Loss (IMF-WS)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 200% of normal energy intake) and fasting (no energy intake).
Intervention: Post-Prandial Meal Tests (Other)
Fasting without Weight Loss (IMF-WS)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 200% of normal energy intake) and fasting (no energy intake).
Intervention: DEXA Scan (Radiation)
Fasting without Weight Loss (IMF-WS)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 200% of normal energy intake) and fasting (no energy intake).
Intervention: Actiheart Calibration (Other)
Fasting without Weight Loss (IMF-WS)
During the intervention phase, participants randomised to this treatment condition will be asked to alternate between 24 hour cycles of feeding (consume 200% of normal energy intake) and fasting (no energy intake).
Intervention: Intermittent Fasting without Weight Loss (Other)
Outcomes
Primary Outcomes
FASN Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
ACADM Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
ChREBP Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
Fasting Plasma Triglyceride Concentration
Time Frame: Baseline - Pre - Post (7 weeks)
Comparison of triglyceride concentration in the blood plasma at rest across all three measurement points to ensure stability in the monitoring phase and examine change during the intervention phase.
Post-Prandial Ghrelin AUC
Time Frame: Pre - Post (3 weeks)
Comparison of the area under the plasma ghrelin curve seen during the 180 minute post-prandial period following a test meal conducted before and after the intervention phase.
NPAS2 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
ANGPTL4 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
Fasting LDL Cholesterol Concentration
Time Frame: Baseline - Pre - Post (7 weeks)
Comparison of LDL cholesterol concentration in the blood plasma at rest across all three measurement points to ensure stability in the monitoring phase and examine change during the intervention phase.
Post-Prandial Glucose AUC
Time Frame: Pre - Post (3 weeks)
Comparison of the area under the plasma glucose curve seen during the 180 minute post-prandial period following a test meal conducted before and after the intervention phase.
Physical Activity Energy Expenditure
Time Frame: Monitoring - Intervention (7 weeks)
Comparison of the mean physical activity energy expenditure values recorded using the Actiheart monitor during the monitoring and intervention phase to see the impact of the three treatments on physically active behaviours.
Physical Activity Intensity
Time Frame: Monitoring - Intervention (7 weeks)
Comparison of the mean physical activity intensity values recorded using the Actiheart monitor during the monitoring and intervention phase to see the impact of the three treatments on physically active behaviours.
Fasting Plasma Insulin Concentration
Time Frame: Baseline - Pre - Post (7 weeks)
Comparison of insulin concentration in the blood plasma at rest across all three measurement points to ensure stability in the monitoring phase and examine change during the intervention phase.
Fasting Total Cholesterol Concentration
Time Frame: Baseline - Pre - Post (7 weeks)
Comparison of total cholesterol concentration in the blood plasma at rest across all three measurement points to ensure stability in the monitoring phase and examine change during the intervention phase.
Body Fat Percentage
Time Frame: Pre - Post (3 weeks)
Comparison of body fat percentage (measured by dual-energy x-ray absorptiometry) from pre-intervention time-point to post-intervention time-point.
Lean Body Mass
Time Frame: Pre - Post (3 weeks)
Comparison of lean body mass (measured by dual-energy x-ray absorptiometry) from pre-intervention time-point to post-intervention time-point.
Fasting Plasma Glucose Concentration
Time Frame: Baseline - Pre - Post (7 weeks)
Comparison of glucose concentration in the blood plasma at rest across all three measurement points to ensure stability in the monitoring phase and examine change during the intervention phase.
Fasting HDL Cholesterol Concentration
Time Frame: Baseline - Pre - Post (7 weeks)
Comparison of HDL cholesterol concentration in the blood plasma at rest across all three measurement points to ensure stability in the monitoring phase and examine change during the intervention phase.
Post-Prandial Insulin AUC
Time Frame: Pre - Post (3 weeks)
Comparison of the area under the plasma insulin curve seen during the 180 minute post-prandial period following a test meal conducted before and after the intervention phase.
Post-Prandial Peptide-YY AUC
Time Frame: Pre - Post (3 weeks)
Comparison of the area under the plasma peptide-YY curve seen during the 180 minute post-prandial period following a test meal conducted before and after the intervention phase.
ADIPO-Q Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
LPL Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
PPARG Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
SIRT1 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
PIK3R1 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
ACACA Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
ATGL Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
Fasting Leptin Concentration
Time Frame: Baseline - Pre - Post (7 weeks)
Comparison of leptin concentration in the blood plasma at rest across all three measurement points to ensure stability in the monitoring phase and examine change during the intervention phase.
Fasting Adiponectin Concentration
Time Frame: Baseline - Pre - Post (7 weeks)
Comparison of adiponectin concentration in the blood plasma at rest across all three measurement points to ensure stability in the monitoring phase and examine change during the intervention phase.
Fasting Resting Metabolic Rate
Time Frame: Baseline - Pre - Post (7 weeks)
Comparison of resting metabolic rate (measured by indirect calorimetry) across all three measurement points to ensure stability in the monitoring phase and examine change during the intervention phase.
CLOCK Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
PER1 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
SREBP1C Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
PRKAA1 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
PNPLA3 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
AKT2 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
UCP2 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
FABP4 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
CRY1 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
LEP Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
IL-6 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
TNF Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
FSP27 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
HSL Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
GLUT-4 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
SIRT3 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
PPARGC1A Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
CIDE-A Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
PDK4 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
IRS1 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
IRS2 Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
IGF1R Gene Expression in Subcutaneous Adipose Tissue
Time Frame: Pre - Post (3 weeks)
Secondary Outcomes
- Post-Prandial Resting Metabolic Rate(Pre-intervention 60, 120 and 180 minutes after meal - post-intervention 60, 120 and 180 minutes after meal (3 weeks))
- Post-Prandial Lipid Oxidation(Pre-intervention 60, 120 and 180 minutes after meal - post-intervention 60, 120 and 180 minutes after meal (3 weeks))
- Fasting Carbohydrate Oxidation(Pre - Post (3 weeks))
- Fasting Lipid Oxidation(Pre - Post (3 weeks))
- Fasting Protein Oxidation(Pre - Post (3 weeks))
- Post-Prandial Carbohydrate Oxidation(Pre-intervention 60, 120 and 180 minutes after meal - post-intervention 60, 120 and 180 minutes after meal (3 weeks))
- Post-Prandial Protein Oxidation(Pre-intervention 60, 120 and 180 minutes after meal - post-intervention 60, 120 and 180 minutes after meal (3 weeks))
Investigators
James Betts
Professor of Metabolic Physiology
University of Bath