The Impact of Intermittent Fasting on Human Metabolism and Cell Autophagy

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.

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