Fasting therapy - old and new perspectives.

Over centuries, mankind had to deal with a steadily changing food supply. Depending on seasonal fluctuations or greater natural disasters, either plenty or little food was available. As a consequence, people in different areas of the world developed sophisticated strategies, e.g., seasonal fasting, to handle and overcome these problems. Possibly, in these early days, people discovered also the healing power of fasting periods. Interestingly, in all religions worldwide we find instructions for and reports on fasting strategies in order to cure body and soul. In Europe, specifically the German physician Otto Buchinger was one of the first to observe and document systematically the effects of fasting on a variety of diseases and to develop a concept of therapeutic fasting [1]. Fasting is defined as the ability to meet the body’s requirements for macroand micronutrients during a limited period of either shortage or absence of food, by using almost exclusively the body’s energy reserves without endangering health [1]. The term ‘fasting’ is often misused. It has to be clearly differentiated between zero calorie diet and starvation. During fasting, intake of food in forms of vegetable broth and vegetable or fruit juice should not exceed 500 kcal per day. Importantly, fasting is the voluntary abstinence from solid food and stimulants (like caffeine or nicotine) for a limited period of time. When fasting is done properly, one should experience a good level of vitality and absence of hunger. It has to be pointed out that fasting is not solely related to caloric restriction but is rather a multimodal treatment program including also mind-body medicine techniques and spiritual components as well as physical activity [1]. The human organism has the physiological ability to switch from exogenous food supply to endogenous nutrient reserves. While liver and muscle glycogen stores are rather limited and normally depleted after 24 h of fasting, energy is mainly derived from fat stores. Protein is mainly used to deliver amino acids for gluconeogenesis in order to provide glucose for the brain. The caloric restriction below 500 kcal per day leads to a complex and orchestrated central and peripheral neuroendocrine response. Fasting triggers cardiovascular, metabolic, and psychological adaptations, which should be monitored during the fasting period [2]. Water-only fasting and several types of modified fasting regimens display some differences, although all are about partial or total interruption of food intake for a limited period of time. They are often mixed up, and the term ‘fasting’ is, unfortunately, sometimes also used for weight-reducing diets, e.g., very low calorie diet (VLCD) with an energy intake up to 600–800 kcal per day. According to the state of health, fasting can be practiced as therapeutic fasting (‘fasting cure’), preventive fasting, and fasting for the healthy (without therapeutic or medical intention). Fasting is accompanied by integral physiological adaptation processes. Overall, metabolism is geared to use mainly fat resources for fueling energy metabolism of the human body during fasting. Because of the absence or very limited supply of carbohydrates, fatty acid oxidation is partly incomplete, which leads to ketogenesis. However, ‘ketone bodies’, such as acetoacetate and 3-hydroxybutyrate, are mainly utilized by skeletal and cardiac muscle but also by the brain for fueling energy metabolism. During the first 3 days of fasting (adaptation phase), protein catabolism is significantly increased, followed by a steadily decrease in order to spare protein. Furthermore, nitrogen is excreted mainly in form of urea, later on as glutamine in order to spare energy. Glutamine is an important substrate for gluconeogenesis in the kidneys. The resulting ammonia ions are important to neutralize keto acids and uric acid in the kidneys. With the increase in prevalence of obesity since the 1970s, fasting became very popular but was often reduced to low or even zero calorie intake. During that time, numerous discussions came up in the scientific community about a potentially