The Impact of Intermittent Fasting on Human Metabolism and Cell Autophagy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The Impact of Intermittent Fasting on Human Metabolism and Cell Autophagy

Conditions
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Excessive Diet Restriction

Intervention / Treatment
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* Behavioral: Alternate day fasting


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Alternate day fasting<br>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<br>* Subjects are requested to fast every other day. Calorie free fluids are allowed.<br>|
| No Intervention: control group<br>control group | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Sensitivity (HOMA-IR) | 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 | 4 weeks (from Baseline to 4 weeks) | 
| Insulin Sensitivity (QUICKI) | QUICKI was calculated by using the following formula: QUICKI= log(FSI)+log (FPG) FSI=fasting serum insulin FPG=fasting plasma glucose | 4 weeks (from Baseline to 4 weeks) | 
| Insulin Sensitivity (ISI-Index) | 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 weeks (from Baseline to 4 weeks) | 
| Insulin Sensitivity (Matsuda-Index) | 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 | 4 weeks (from Baseline to 4 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Pressure (Systolic and Diastolic) | Change of blood pressure from Baseline to 4 weeks | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alternate Day Fasting