The Impact of Intermittent Fasting on Human Metabolism and Cell Autophagy (InterFast)

• ClinicalTrials.gov Identifier: NCT02673515
• Recruitment Status: Completed
• First Posted: February 4, 2016
• Results First Posted: May 28, 2020
• Last Update Posted: May 28, 2020
• Sponsor: Medical University of Graz
• Collaborator: University of Graz
• Information provided by (Responsible Party): Medical University of Graz

Study Description

Brief Summary:

InterFast is a Cohort study with an embedded randomized controlled pilot trial. Study participants will be healthy subjects and subjects who already practice Alternate Day Fasting. The trial will include 100 participants (50 Participants in Alternate Day Fasting group and 50 participants in the control group). Those participants in the control group will be asked to participate in a short randomized controlled trial, where they will be either allocated to an Alternative Day Fasting group or another control visit.

Condition or disease	Intervention/treatment	Phase
Excessive Diet Restriction	Behavioral: Alternate day fasting	Not Applicable

Detailed Description:

Intermittent fasting is a dietary regimen defined by alternating fasting and "feeding" cycles. In addition to caloric restriction (a dietary regimen limited to a daily food intake lower than one's daily caloric needs) only, intermittent fasting seems to activate cell autophagy (cellular "recycling" program) which potentially increases cellular stress resistance and removes accumulated molecules that are potentially toxic. In fact, mice maintained on intermittent fasting without decreased overall food intake show effects on body weight reduction that equal and in some cases even exceed those of calorie restriction. However, additionally, intermittent fasting combined with even a high-fat diet in the feeding periods protects mice from obesity, hyperinsulinemia, hepatic steatosis, and inflammation compared to controls that are fed an ad libitum high-fat diet despite the same calorie intake, making this intermittent fasting regimen a promising approach to reduce morbidity and mortality in various species.

The best described and most widely practiced version of intermittent fasting is the "alternate day diet" or "alternate day fasting" (ADF). In animal models, ADF consists of an ad libitum "feed day" alternated with a 100% restriction "fast day". However in humans, this is often modified to allow a small amount of food consumption on the "fast day" (e.g. 25% of the individual´s energy needs). Findings from recent modified ADF studies showed significant reductions in body weight.

However, knowledge about the molecular effects of the alternate day diet on human metabolism or autophagy is still scarce since detailed analyses of molecular and metabolic parameters remain unexplored, especially in healthy individuals. The overarching aim of this research project is to elucidate in which extent alternate day fasting (and thereby intermittent fasting) influences human physiology in healthy individuals in both short and long term. The secondary objective of this study is to define novel molecular markers of aging and age-related diseases.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: The Impact of Intermittent Fasting on Human Metabolism and Cell Autophagy
• Study Start Date: April 2015
• Actual Primary Completion Date: September 2, 2019
• Actual Study Completion Date: September 2, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Alternate day fasting; Subjects are requested to alternate fast for 4 weeks (alternate an ad libitum "feed day" with a 100% restriction "fast day").	Behavioral: Alternate day fasting; Subjects are requested to fast every other day. Calorie free fluids are allowed.
No Intervention: control group; control group

Outcome Measures

Primary Outcome Measures :

1. Insulin Sensitivity (HOMA-IR) [ Time Frame: 4 weeks (from Baseline to 4 weeks) ]

   HOMA-Index was calculated by using the following formula:

   HOMA-IR= FPG(mmol/l)*FSI (U/l)/22.5 FSI=fasting serum insulin FPG=fasting plasma glucose

2. Insulin Sensitivity (QUICKI) [ Time Frame: 4 weeks (from Baseline to 4 weeks) ]
   QUICKI was calculated by using the following formula: QUICKI= log(FSI)+log (FPG) FSI=fasting serum insulin FPG=fasting plasma glucose
3. Insulin Sensitivity (ISI-Index) [ Time Frame: 4 weeks (from Baseline to 4 weeks) ]
   ISI was calculated by using the following formula: ISI=0,222-0,00333 x BMI-0,0000779 x Ins120-0,000422 x age FSI=fasting serum insulin FPG=fasting plasma glucose
4. Insulin Sensitivity (Matsuda-Index) [ Time Frame: 4 weeks (from Baseline to 4 weeks) ]

   Matsuda index was calculated by using the following formula:

   Matsuda-Index = 10000√(FPG∗FSI)∗(mean glucose*mean insulin) FSI=fasting serum insulin FPG=fasting plasma glucose

Secondary Outcome Measures :

1. Blood Pressure (Systolic and Diastolic) [ Time Frame: 4 weeks ]
   Change of blood pressure from Baseline to 4 weeks

Eligibility Criteria

• Ages Eligible for Study: 35 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Body mass index in the range of 22.0 - 27.0 kg/m2,
• Fasting blood glucose <110mg/dL (without medication)
• LDL-cholesterol <180 mg/dL (without medication)
• Blood pressure <140/90 mmHg (without medication)
• Stable weight (change <± 10%) for 3 months immediately prior to the study,
• No history of metabolic disorders or cardiovascular disease
• No acute or chronic inflammatory disorder
• No current medications to regulate blood sugar, blood pressure or lipids or hormones
• No heavy drinking (more than 15 drinks/week)
• No use of tobacco or recreational drugs within past 5 years
• No dietary restrictions (e.g. vegetarianism and vegan)

Exclusion Criteria:

• Known Malignancy
• Women who are pregnant, breast-feeding or trying to become pregnant
• History of any chronic disease process that could interfere with interpretation of study results
• Women or men on hormonal supplementation or anti-conceptive hormonal medication for at least 2 months
• Therapy with antidepressants within past 6 months
• Regular therapy with acetylsalicylic acid

Contacts and Locations

Locations

Austria

Dept. of Internal Medicine, Medical University of Graz

Graz, Austria, 8036

Sponsors and Collaborators

Medical University of Graz

University of Graz

Investigators

• Principal Investigator: Harald Sourij, MD; Medical University of Graz, Auenbruggerplatz 15
• Study Chair: Frank Madeo, PhD; Karl Franzens University Graz, Austria
• Study Chair: Thomas R Pieber, MD; Medical University Graz, Austria

  Study Documents (Full-Text)

Documents provided by Medical University of Graz:

Study Protocol  [PDF] June 1, 2018

No Statistical Analysis Plan (SAP) exists for this study.

More Information

Publications of Results:

Stekovic S, Hofer SJ, Tripolt N, Aon MA, Royer P, Pein L, Stadler JT, Pendl T, Prietl B, Url J, Schroeder S, Tadic J, Eisenberg T, Magnes C, Stumpe M, Zuegner E, Bordag N, Riedl R, Schmidt A, Kolesnik E, Verheyen N, Springer A, Madl T, Sinner F, de Cabo R, Kroemer G, Obermayer-Pietsch B, Dengjel J, Sourij H, Pieber TR, Madeo F. Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans. Cell Metab. 2019 Sep 3;30(3):462-476.e6. doi: 10.1016/j.cmet.2019.07.016. Epub 2019 Aug 27. Erratum In: Cell Metab. 2020 Apr 7;31(4):878-881.

Other Publications:

Tripolt NJ, Stekovic S, Aberer F, Url J, Pferschy PN, Schroder S, Verheyen N, Schmidt A, Kolesnik E, Narath SH, Riedl R, Obermayer-Pietsch B, Pieber TR, Madeo F, Sourij H. Intermittent Fasting (Alternate Day Fasting) in Healthy, Non-obese Adults: Protocol for a Cohort Trial with an Embedded Randomized Controlled Pilot Trial. Adv Ther. 2018 Aug;35(8):1265-1283. doi: 10.1007/s12325-018-0746-5. Epub 2018 Jul 25.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Allaf M, Elghazaly H, Mohamed OG, Fareen MFK, Zaman S, Salmasi AM, Tsilidis K, Dehghan A. Intermittent fasting for the prevention of cardiovascular disease. Cochrane Database Syst Rev. 2021 Jan 29;1(1):CD013496. doi: 10.1002/14651858.CD013496.pub2.

• Responsible Party: Medical University of Graz
• ClinicalTrials.gov Identifier: NCT02673515
• Other Study ID Numbers: HS-2014-03
• First Posted: February 4, 2016
• Results First Posted: May 28, 2020
• Last Update Posted: May 28, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Medical University of Graz:

Alternate Day Fasting