Only few studies document longer periods of fasting in large cohorts including non-obese participants. The aim of this study was to document prospectively the safety and any changes in basic health and well-being indicators during Buchinger periodic fasting within a specialised clinic. In a one-year observational study 1422 subjects participated in a fasting program consisting of fasting periods of between 4 and 21 days. Subjects were grouped in fasting period lengths of 5, 10, 15 and 20±2 days. The participants fasted according to the Buchinger guidelines with a daily caloric intake of 200–250 kcal accompanied by a moderate-intensity lifestyle program. Clinical parameters as well as adverse effects and well-being were documented daily. Blood examinations before and at the end of the fasting period complemented the pre-post analysis using mixed-effects linear models. Significant reductions in weight, abdominal circumference and blood pressure were observed in the whole group (each p<0.001). A beneficial modulating effect of fasting on blood lipids, glucoregulation and further general health-related blood parameters was shown. In all groups, fasting led to a decrease in blood glucose levels to low norm range and to an increase in ketone bodies levels (each p<0.001), documenting the metabolic switch. An increase in physical and emotional well-being (each p<0.001) and an absence of hunger feeling in 93.2% of the subjects supported the feasibility of prolonged fasting. Among the 404 subjects with pre-existing health-complaints, 341 (84.4%) reported an improvement. Adverse effects were reported in less than 1% of the participants. The results from 1422 subjects showed for the first time that Buchinger periodic fasting lasting from 4 to 21 days is safe and well tolerated. It led to enhancement of emotional and physical well-being and improvements in relevant cardiovascular and general risk factors, as well as subjective health complaints.

Fasting for medical purpose (fasting therapy) has a long tradition in Europe and is established as a defined therapeutic approach in specialized fasting hospitals or within clinical departments for integrative medicine. In 2002, the first guidelines for fasting therapy were published following an expert consensus conference; here we present a revised update elaborated by an expert panel. Historical aspects and definitions, indications, methods, forms, and accompanying procedures of fasting as well as safety and quality criteria of fasting interventions are described. Fasting has shown beneficial effects in various chronic diseases with highest level of evidence for rheumatic diseases. Preliminary clinical and observational data and recently revealed mechanisms of fasting and caloric restriction indicate beneficial effects of fasting also in other chronic conditions such as metabolic diseases, pain syndromes, hypertension, chronic inflammatory diseases, atopic diseases, and psychosomatic disorders. Fasting can also be applied for preventing diseases in healthy subjects. In order to guarantee successful use of fasting and to ensure adherence of all safety and quality standards it is mandatory that all interventions during fasting are guided/accompanied by physicians/therapists trained and certified in fasting therapy.

In recent years a revival of interest has emerged in the health benefits of intermittent fasting and long-term fasting, as well as of other related nutritional strategies. In addition to meal size and composition a new focus on time and frequency of meals has gained attention. The present review will investigate the effects of the main forms of fasting, activating the metabolic switch from glucose to fat and ketones (G-to-K), starting 12-16 h after cessation or strong reduction of food intake. During fasting the deactivation of mTOR regulated nutrient signalling pathways and activation of the AMP protein kinase trigger cell repair and inhibit anabolic processes. Clinical and animal studies have clearly indicated that modulating diet and meal frequency, as well as application of fasting patterns, e.g. intermittent fasting, periodic fasting, or long-term fasting are part of a new lifestyle approach leading to increased life and health span, enhanced intrinsic defences against oxidative and metabolic stresses, improved cognition, as well as a decrease in cardiovascular risk in both obese and non-obese subjects. Finally, in order to better understand the mechanisms beyond fasting-related changes, human studies as well as non-human models closer to human physiology may offer useful clues. KEY-MESSAGES 1. Biochemical changes during fasting are characterised by a glucose to ketone switch, leading to a rise of ketones, advantageously used for brain energy, with consequent improved cognition. 2. Ketones reduce appetite and help maintain effective fasting. 3. Application of fasting patterns increases healthy life span and defences against oxidative and metabolic stresses. 4. Today's strategies for the use of therapeutic fasting are based on different protocols, generally relying on intermittent fasting, of different duration and calorie intake. 5. Long-term fasting, with durations between 5 and 21 days can be successfully repeated in the course of a year.

Fasting is increasingly popular to manage metabolic and inflammatory diseases. Despite the role that the human gut microbiota plays in health and diseases, little is known about its composition and functional capacity during prolonged fasting when the external nutrient supply is reduced or suppressed. We analysed the effects of a 10-d periodic fasting on the faecal microbiota of fifteen healthy men. Participants fasted according to the peer-reviewed Buchinger fasting guidelines, which involve a daily energy intake of about 1046 kJ (250 kcal) and an enema every 2 d. Serum biochemistry confirmed the metabolic switch from carbohydrates to fatty acids and ketones. Emotional and physical well-being were enhanced. Faecal 16S rRNA gene amplicon sequencing showed that fasting caused a decrease in the abundance of bacteria known to degrade dietary polysaccharides such as Lachnospiraceae and Ruminococcaceae. There was a concomitant increase in Bacteroidetes and Proteobacteria (Escherichia coli and Bilophila wadsworthia), known to use host-derived energy substrates. Changes in taxa abundance were associated with serum glucose and faecal branched-chain amino acids (BCAA), suggesting that fasting-induced changes in the gut microbiota are associated with host energy metabolism. These effects were reversed after 3 months. SCFA levels were unchanged at the end of the fasting. We also monitored intestinal permeability and inflammatory status. IL-6, IL-10, interferon γ and TNFα levels increased when food was reintroduced, suggesting a reactivation of the postprandial immune response. We suggest that changes in the gut microbiota are part of the physiological adaptations to a 10-d periodic fasting, potentially influencing its beneficial health effects.

This prospective observational trial investigated effects and safety of periodic fasting in subjects with and without type 2 diabetes mellitus (T2DM). The primary end point was set as the change of fatty liver index (FLI) as a surrogate parameter of non-alcoholic fatty liver disease (NAFLD). Six-hundred and ninety-seven subjects (38 with T2DM) were enrolled. A baseline FLI ≥ 60 (the threshold for fatty liver) was found in 264 subjects (37.9%). The mean duration of fasting was 8.5 ± 4.0 days (range 6–38). FLI decreased significantly (−14.02 ± 11.67; p < 0.0001), with a larger effect in individuals with T2DM (−19.15 ± 11.0; p < 0.0001; p = 0.002 compared to non-diabetic subjects). Body mass index (BMI) decreased by −1.51 ± 0.82 kg/m2, and 49.9% of the subjects lost ≥5% body weight. After fasting, nearly half of the 264 subjects with FLI ≥ 60 (highest risk category) shifted to a lower category. The improvement of FLI correlated with the number of fasting days (r = −0.20, p < 0.0001) and with the magnitude of BMI reduction (r = 0.14, p = 0.0001). Periodic fasting with concomitant weight reduction leads to significant rapid improvement of FLI in subjects with and without T2DM.