The Impact of Intermittent Fasting on Human Metabolism and Cell Autophagy

Not Applicable

Completed

Conditions: Excessive Diet Restriction

Interventions: Behavioral: Alternate day fasting

Registration Number: NCT02673515

Lead Sponsor: Medical University of Graz

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Alternate day fasting	Alternate day fasting	Subjects are requested to alternate fast for 4 weeks (alternate an ad libitum "feed day" with a 100% restriction "fast day").

Primary Outcome Measures

Name	Time	Method
Insulin Sensitivity (ISI-Index)	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
Insulin Sensitivity (Matsuda-Index)	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
Insulin Sensitivity (HOMA-IR)	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
Insulin Sensitivity (QUICKI)	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