In humans, fasting is achieved by ingesting no (or minimal amounts of) food and caloric liquids for periods that typically range from 12 hours to 3 weeks. Its constitutive part of different societies and epochs also manifested in the form of religious rituals, such as Ramadan or Christian Orthodox fasting, and, more recently, as a tool to make a political statement or to protest.
The effects of fasting and caloric restriction on metabolism have been largely studied and involve complex and interrelated mechanisms, including oxidative stress, protein degradation, autophagy, reduction of advance glycation end-products, as well as profound hormonal and metabolic changes. Fasting regimens might ameliorate disease processes and improve functional outcome in disorders like cancer, myocardial infarction, diabetes, and stroke , as shown in animal models. Recent results suggested that cycles of fasting modulate key regulators of cellular protection and tissue regeneration, but also provide a potential therapy to alleviate the immunosuppression or immunosenescence caused by chemotherapy treatment or aging.
On the basis of the results from available literature suggesting a profound effect of complete fasting on some hemostatic parameters, we aim to study the extent and the dynamic of complete prolonged fasting on the main components of the hemostatic system, including primary and secondary hemostasis, fibrinolysis, and endothelial function. Moreover, we aim to confirm in humans the expectably significant changes in gut microbiota composition, metabolites, and characteristics after fasting, also to eventually explore the link between these changes and the hemostatic system. In our proof-of-concept study, we will enroll 15 otherwise healthy non-obese male subjects, who will be asked to fast for a total of 3 days. Only non-caloric liquids will be allowed. Since the main aim is to study not only the net effect on the outcomes of interest after this period, but also the dynamic of changes, blood and stool material will be collected on a daily basis before, during, and after the fasting period. To the best of our knowledge, only very few interventional studies focused on the effects of (intermittent or short-course [<24 h]) fasting on human gut microbiota, and on the interconnections between gut microbiota and hemostasis. Therefore, this topic will be of extreme interest for the scientific community as it may help the generation of hypotheses regarding specific mechanisms of disease in a controlled setting, in which additional confounders, beyond inter-individual variability, will be minimized.