Impacts of Intermittent Fasting on Energy Balance and Associated Health Outcomes

NCT02498002 | Completed

• 1 other identifier: IMF-02
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

1. 1.Daily calorie restriction - Reduce energy intake by 25% on a daily basis
2. 2.IMF with weight loss - Alternate between 24 hour cycles of fasting and feeding with 150% of normal intake when feeding
3. 3.IMF without weight loss - Alternate between 24 hour cycles of fasting and feeding with 200% of normal intake when feeding

Conditions

Obesity; Type 2 Diabetes

Keywords

Diet; Fasting; Intermittent Fasting; Alternate-day Fasting; Physical Activity; Glucose; Insulin; Appetite

Outcome Measures

Primary Outcomes (51)

• Body Fat Percentage

  Comparison of body fat percentage (measured by dual-energy x-ray absorptiometry) from pre-intervention time-point to post-intervention time-point.

  Pre - Post (3 weeks)

• Lean Body Mass

  Comparison of lean body mass (measured by dual-energy x-ray absorptiometry) from pre-intervention time-point to post-intervention time-point.

  Pre - Post (3 weeks)

• Fasting Plasma Glucose Concentration

  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.

  Baseline - Pre - Post (7 weeks)

• Fasting Plasma Insulin Concentration

  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.

  Baseline - Pre - Post (7 weeks)

• Fasting Plasma Triglyceride Concentration

  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.

  Baseline - Pre - Post (7 weeks)

• Fasting Total Cholesterol Concentration

  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.

  Baseline - Pre - Post (7 weeks)

• Fasting LDL Cholesterol Concentration

  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.

  Baseline - Pre - Post (7 weeks)

• Fasting HDL Cholesterol Concentration

  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.

  Baseline - Pre - Post (7 weeks)

• Fasting Leptin Concentration

  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.

  Baseline - Pre - Post (7 weeks)

• Fasting Adiponectin Concentration

  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.

  Baseline - Pre - Post (7 weeks)

• Fasting Resting Metabolic Rate

  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.

  Baseline - Pre - Post (7 weeks)

• Post-Prandial Glucose AUC

  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.

  Pre - Post (3 weeks)

• Post-Prandial Insulin AUC

  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.

  Pre - Post (3 weeks)

• Post-Prandial Ghrelin AUC

  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.

  Pre - Post (3 weeks)

• Post-Prandial Peptide-YY AUC

  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.

  Pre - Post (3 weeks)

• Physical Activity Energy Expenditure

  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.

  Monitoring - Intervention (7 weeks)

• Physical Activity Intensity

  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.

  Monitoring - Intervention (7 weeks)

• CLOCK Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• NPAS2 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• PER1 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• CRY1 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• LEP Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• ADIPO-Q Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• IL-6 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• TNF Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• LPL Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• FABP4 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• PPARG Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• PPARGC1A Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• SREBP1C Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• FSP27 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• PRKAA1 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• ANGPTL4 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• HSL Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• ATGL Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• PNPLA3 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• CIDE-A Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• GLUT-4 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• AKT2 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• PDK4 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• SIRT1 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• SIRT3 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• UCP2 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• IGF1R Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• IRS1 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• IRS2 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• PIK3R1 Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• ChREBP Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• ACACA Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• FASN Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

• ACADM Gene Expression in Subcutaneous Adipose Tissue

  Pre - Post (3 weeks)

Secondary Outcomes (7)

• Fasting Carbohydrate Oxidation

  Pre - Post (3 weeks)

• Fasting Lipid Oxidation

  Pre - Post (3 weeks)

• Fasting Protein Oxidation

  Pre - Post (3 weeks)

• 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 Carbohydrate Oxidation

  Pre-intervention 60, 120 and 180 minutes after meal - post-intervention 60, 120 and 180 minutes after meal (3 weeks)

Study Arms (3)

Daily Calorie Restriction (DCR)

ACTIVE COMPARATOR

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.

Device: Physical Activity Monitoring (Actiheart); Other: Energy Intake Monitoring; Other: Body Weight Monitoring; Procedure: Intravenous Cannulation; Procedure: Adipose Tissue Biopsy; Drug: Lidocaine Hydrochloride; Other: Post-Prandial Meal Tests; Radiation: DEXA Scan; Other: Actiheart Calibration; Other: Daily Calorie Restriction

Fasting with Weight Loss (IMF-WL)

EXPERIMENTAL

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).

Device: Physical Activity Monitoring (Actiheart); Other: Energy Intake Monitoring; Other: Body Weight Monitoring; Procedure: Intravenous Cannulation; Procedure: Adipose Tissue Biopsy; Drug: Lidocaine Hydrochloride; Other: Post-Prandial Meal Tests; Radiation: DEXA Scan; Other: Actiheart Calibration; Other: Intermittent Fasting with Weight Loss

Fasting without Weight Loss (IMF-WS)

EXPERIMENTAL

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).

Device: Physical Activity Monitoring (Actiheart); Other: Energy Intake Monitoring; Other: Body Weight Monitoring; Procedure: Intravenous Cannulation; Procedure: Adipose Tissue Biopsy; Drug: Lidocaine Hydrochloride; Other: Post-Prandial Meal Tests; Radiation: DEXA Scan; Other: Actiheart Calibration; Other: Intermittent Fasting without Weight Loss

Interventions

Physical Activity Monitoring (Actiheart) DEVICE

Monitor physical activity using an Actiheart monitor during the required periods.

Daily Calorie Restriction (DCR); Fasting with Weight Loss (IMF-WL); Fasting without Weight Loss (IMF-WS)

Energy Intake Monitoring OTHER

Monitor energy intake by weighing and recording all foods/drinks consumed during the required periods.

Daily Calorie Restriction (DCR); Fasting with Weight Loss (IMF-WL); Fasting without Weight Loss (IMF-WS)

Body Weight Monitoring OTHER

Monitor body weight during monitoring phase to ensure stability despite other monitoring activities.

Daily Calorie Restriction (DCR); Fasting with Weight Loss (IMF-WL); Fasting without Weight Loss (IMF-WS)

Intravenous Cannulation PROCEDURE

Fitting of an intravenous cannula to a vein on the forearm for blood sampling during laboratory protocols.

Daily Calorie Restriction (DCR); Fasting with Weight Loss (IMF-WL); Fasting without Weight Loss (IMF-WS)

Adipose Tissue Biopsy PROCEDURE

This is an optional feature which if included involves the removal of a 0.5 gram sample of adipose tissue from just below the skin using a needle.

Daily Calorie Restriction (DCR); Fasting with Weight Loss (IMF-WL); Fasting without Weight Loss (IMF-WS)

Lidocaine Hydrochloride DRUG

The anaesthetic that will be used to numb the site of the adipose tissue biopsy in the event it is included.

Daily Calorie Restriction (DCR); Fasting with Weight Loss (IMF-WL); Fasting without Weight Loss (IMF-WS)

Post-Prandial Meal Tests OTHER

Consume two successive meals with regular blood samples throughout the ensuing hours (2-3 hours each).

Daily Calorie Restriction (DCR); Fasting with Weight Loss (IMF-WL); Fasting without Weight Loss (IMF-WS)

DEXA Scan RADIATION

Undergo a dual energy x-ray absorptiometry scan to examine body composition.

Daily Calorie Restriction (DCR); Fasting with Weight Loss (IMF-WL); Fasting without Weight Loss (IMF-WS)

Actiheart Calibration OTHER

Submaximal treadmill test to calibrate monitoring equipment.

Daily Calorie Restriction (DCR); Fasting with Weight Loss (IMF-WL); Fasting without Weight Loss (IMF-WS)

Daily Calorie Restriction OTHER

Reduce energy intake by 25% on a daily basis.

Daily Calorie Restriction (DCR)

Intermittent Fasting with Weight Loss OTHER

Alternate between 24 hour cycles of fasting and feeding with 150% of normal intake when feeding.

Fasting with Weight Loss (IMF-WL)

Intermittent Fasting without Weight Loss OTHER

Alternate between 24 hour cycles of fasting and feeding with 200% of normal intake when feeding.

Fasting without Weight Loss (IMF-WS)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Bath: lead

Study Sites (1)

University of Bath

Bath, Somerset, BA2 7AY, United Kingdom

Location

Related Publications (1)

• Templeman I, Thompson D, Gonzalez J, Walhin JP, Reeves S, Rogers PJ, Brunstrom JM, Karagounis LG, Tsintzas K, Betts JA. Intermittent fasting, energy balance and associated health outcomes in adults: study protocol for a randomised controlled trial. Trials. 2018 Feb 2;19(1):86. doi: 10.1186/s13063-018-2451-8.

  PMID: 29394908 DERIVED

MeSH Terms

Conditions

Obesity; Diabetes Mellitus, Type 2; Fasting; Intermittent Fasting; Motor Activity; Insulin Resistance

Interventions

Lidocaine; Absorptiometry, Photon

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Feeding Behavior; Behavior; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Radiography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Densitometry; Photometry; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• James A Betts, BSc., Ph.D

  Fellow of the American College of Sports Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Metabolic Physiology

Study Record Dates

• First Submitted: July 6, 2015
• First Posted: July 15, 2015
• Study Start: May 1, 2015
• Primary Completion: September 4, 2018
• Study Completion: September 28, 2018
• Last Updated: April 18, 2023

Record last verified: 2023-04

Locations

GB (1)