Long-Term Fasting-Induced Ketosis in 1610 Subjects: Metabolic Regulation and Safety.

BACKGROUND: There is a growing consensus that fasting-induced ketosis has beneficial effects on human physiology. Despite these compelling benefits, fasting-induced ketosis raises concerns in some clinicians because it is often inappropriately compared with the pathologic uncontrolled ketone production in diabetic ketoacidosis. The determinants of the inter-individual differences in the intensity of ketosis during long-term fasting is unknown. METHODS: We monitored daily variations in fasting ketonemia, as well as ketonuria, which is less invasive, in a large cohort of 1610 subjects, fasting between 4 and 21 days with the Buchinger Wilhelmi program, minimally supplemented with ~75-250 kcal (daily fruit juice, vegetable soup, and honey). RESULTS: Ketonuria was detected in more than 95% of fasting subjects from day 4 onwards. Subjects consuming only soups, without fruit juice or honey, exhibited reduced caloric intake (72 kcal instead of 236 kcal) and carbohydrate intake (15.6 g instead of 56.5 g), leading to more intense ketonuria. Participants with high ketonuria were, in the majority, males, young, had a higher body weight, and had lower HDL-C and urea values. They had a larger decrease in blood glucose, glycated haemoglobin levels, body weight, and waist circumference. Furthermore, in the high-ketonuria group, a larger increase in blood uric acid concentration was observed. CONCLUSION: Our study showed that long-term fasting triggered ketosis, never reaching pathological levels, and that ketosis is influenced by age, gender, health, and the level of physical activity. Furthermore, it is modulated but not suppressed by minimal carbohydrate intake. Our study paves the way for better understanding how supplementation can modulate the therapeutic effects and tolerability of long-term fasting.

World's Longest Medically Documented Repeated Fasting History in a 92 Years Old Man Who Fasted 21 Days Yearly for 45 Years: A Case Report.

Case presentation: Scientific documentation on lifelong repeated cycles of long-term fasting doesn't exist. We report the case of a 92-year-old man who fasted 3 weeks yearly for 45 years. Results: Body weight and clinical parameters showed cyclic variations, returning to baseline after food reintroduction. Biological age analysis indicated that the patient was 5.9 years younger than his chronological age. Mental and physical health tests documented the absence of frailty, that the patient could function independently, had excellent cognitive functions, and a good mobility. Conclusion: It can be reasonably assumed that this subject have had protective effects from his yearly fasting.

Improvements during long-term fasting in patients with long COVID - a case series and literature review.

Background: Post-acute sequelae of a severe acute respiratory syndrome coronavirus 2 infection, also known as long COVID, comprises a variety of symptoms that impair the quality of life. This represents a growing public health burden, with millions of individuals worldwide affected. Case description: We present a case series of 14 COVID-19 patients with post-acute symptoms who underwent medically supervised long-term fasting (6 to 16 days) according to the peer-reviewed Buchinger Wilhelmi protocol. The EQ-5D-5L questionnaire and visual scales were used to evaluate the intensity of the symptoms, retrospectively during the acute phase, and prospectively before and after long-term fasting. Blood tests were also performed before and after fasting. Thirteen patients reported that fasting caused an enhancement in their perceived overall health. Only one patient had no improvement. Both frequent (fatigue, breathlessness, muscle and joint pains) and less frequent (cognitive impairment, smell and taste disorders) sequelae ameliorated. Body weight and other risk factors for cardiometabolic diseases like blood pressure, blood glucose, total cholesterol, low-density-lipoprotein cholesterol, and triglycerides were reduced. No severe side effects occurred. Discussion: This case series reports beneficial changes in self-perceived symptoms in patients with long COVID after long-term fasting. This highlights the potential of long-term fasting as an effective intervention for managing and treating long COVID.

Remodelling of the intestinal ecosystem during caloric restriction and fasting.

Benefits of fasting and caloric restriction on host metabolic health are well established, but less is known about the effects on the gut microbiome and how this impacts renewal of the intestinal mucosa. What has been repeatedly shown during fasting, however, is that bacteria utilising host-derived substrates proliferate at the expense of those relying on dietary substrates. Considering the increased recognition of the gut microbiome's role in maintaining host (metabolic) health, disentangling host-microbe interactions and establishing their physiological relevance in the context of fasting and caloric restriction is crucial. Such insights could aid in moving away from associations of gut bacterial signatures with metabolic diseases consistently reported in observational studies to potentially establishing causality. Therefore, this review aims to summarise what is currently known or still controversial about the interplay between fasting and caloric restriction, the gut microbiome and intestinal tissue physiology.

Long-term fasting: Multi-system adaptations in humans (GENESIS) study-A single-arm interventional trial.

Fasting provokes fundamental changes in the activation of metabolic and signaling pathways leading to longer and healthier lifespans in animal models. Although the involvement of different metabolites in fueling human fasting metabolism is well known, the contribution of tissues and organs to their supply remains partly unclear. Also, changes in organ volume and composition remain relatively unexplored. Thus, processes involved in remodeling tissues during fasting and food reintroduction need to be better understood. Therefore, this study will apply state-of-the-art techniques to investigate the effects of long-term fasting (LF) and food reintroduction in humans by a multi-systemic approach focusing on changes in body composition, organ and tissue volume, lipid transport and storage, sources of protein utilization, blood metabolites, and gut microbiome profiles in a single cohort. This is a prospective, single-arm, monocentric trial. One hundred subjects will be recruited and undergo 9 ± 3 day-long fasting periods (250 kcal/day). We will assess changes in the composition of organs, bones and blood lipid profiles before and after fasting, as well as high-density lipoprotein (HDL) transport and storage, untargeted metabolomics of peripheral blood mononuclear cells (PBMCs), protein persulfidation and shotgun metagenomics of the gut microbiome. The first 32 subjects, fasting for 12 days, will be examined in more detail by magnetic resonance imaging (MRI) and spectroscopy to provide quantitative information on changes in organ volume and function, followed by an additional follow-up examination after 1 and 4 months. The study protocol was approved by the ethics board of the State Medical Chamber of Baden-Württemberg on 26.07.2021 and registered at ClinicalTrials.gov (NCT05031598). The results will be disseminated through peer-reviewed publications, international conferences and social media. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT05031598].

Excretion of Heavy Metals and Glyphosate in Urine and Hair Before and After Long-Term Fasting in Humans.

Background: Dietary exposure to environmental pollutants in humans is an important public health concern. While long-term fasting interrupts the dietary exposure to these substances, fat mobilization as an energy source may also release bioaccumulated substances. This was, to our knowledge, only investigated in obese people decades ago. This study explored the effects of 10-days fasting on the excretion of heavy metals and glyphosate. Methods: Urinary levels of arsenic, chromium, cobalt, lead, nickel, mercury and glyphosate were measured before and after 10 fasting days in 109 healthy subjects. Additionally, hair analysis was done before and ten weeks after fasting in 22 subjects. Results: Fasting caused a decrease in body weight, and in urinary arsenic (by 72%) and nickel (by 15%) concentrations. A decrease in lead hair concentrations (by 30%) was documented. Urinary mercury levels were unchanged for chromium, cobalt and glyphosate, which were undetectable in most of the subjects. Additionally, fatigue, sleep disorders, headache and hunger were reduced. Body discomfort symptoms diminished four weeks after food reintroduction. Conclusions: The results of this study provide the first insights into the changes in heavy metal excretion caused by long-term fasting. Further studies focusing on the kinetics of efflux between different compartments of the body are needed. Clinical Trial Registration: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016657, identifier: DRKS00016657.

Is muscle and protein loss relevant in long-term fasting in healthy men? A prospective trial on physiological adaptations.

BACKGROUND: Fasting is attracting an increasing interest as a potential strategy for managing diseases, including metabolic disorders and complementary cancer therapy. Despite concerns of clinicians regarding protein catabolism and muscle loss, evidence-based clinical data in response to long-term fasting in healthy humans are scarce. The objective of this study was to measure clinical constants, metabolic, and muscular response in healthy men during and after a 10 day fast combined with a physical activity programme. METHODS: Sixteen men (44 ± 14 years; 26.2 ± 0.9 kg/m2 ) fasted with a supplement of 200-250 kcal/day and up to 3 h daily low-intensity physical activity according to the peer-reviewed Buchinger Wilhelmi protocol. Changes in body weight (BW) and composition, basal metabolic rate (BMR), physical activity, muscle strength and function, protein utilization, inflammatory, and metabolic status were assessed during the 10 day fast, the 4 days of food reintroduction, and at 3 month follow-up. RESULTS: The 10 day fast decreased BW by 7% (-5.9 ± 0.2 kg, P < 0.001) and BMR by 12% (P < 0.01). Fat mass and lean soft tissues (LST) accounted for about 40% and 60% of weight loss, respectively, -2.3 ± 0.18 kg and -3.53 ± 0.13 kg, P < 0.001. LST loss was explained by the reduction in extracellular water (44%), muscle and liver glycogen and associated water (14%), and metabolic active lean tissue (42%). Plasma 3-methyl-histidine increased until Day 5 of fasting and then decreased, suggesting that protein sparing might follow early proteolysis. Daily steps count increased by 60% (P < 0.001) during the fasting period. Strength was maintained in non-weight-bearing muscles and increased in weight-bearing muscles (+33%, P < 0.001). Glycaemia, insulinemia, blood lipids, and blood pressure dropped during the fast (P < 0.05 for all), while non-esterified fatty acids and urinary beta-hydroxybutyrate increased (P < 0.01 for both). After a transient reduction, inflammatory cytokines returned to baseline at Day 10 of fasting, and LST were still lower than baseline values (-2.3% and -3.2%, respectively; P < 0.05 for both). CONCLUSIONS: A 10 day fast appears safe in healthy humans. Protein loss occurs in early fast but decreases as ketogenesis increases. Fasting combined with physical activity does not negatively impact muscle function. Future studies will need to confirm these first findings.

Effects of acyl-coenzyme A binding protein (ACBP)/diazepam-binding inhibitor (DBI) on body mass index.

In mice, the plasma concentrations of the appetite-stimulatory and autophagy-inhibitory factor acyl-coenzyme A binding protein (ACBP, also called diazepam-binding inhibitor, DBI) acutely increase in response to starvation, but also do so upon chronic overnutrition leading to obesity. Here, we show that knockout of Acbp/Dbi in adipose tissue is sufficient to prevent high-fat diet-induced weight gain in mice. We investigated ACBP/DBI plasma concentrations in several patient cohorts to discover a similar dual pattern of regulation. In relatively healthy subjects, ACBP/DBI concentrations independently correlated with body mass index (BMI) and age. The association between ACBP/DBI and BMI was lost in subjects that underwent major weight gain in the subsequent 3-9 years, as well as in advanced cancer patients. Voluntary fasting, undernutrition in the context of advanced cancer, as well as chemotherapy were associated with an increase in circulating ACBP/DBI levels. Altogether, these results support the conclusion that ACBP/DBI may play an important role in body mass homeostasis as well as in its failure.

Long-term fasting improves lipoprotein-associated atherogenic risk in humans.

PURPOSE: Dyslipidemia is a major health concern associated with an increased risk of cardiovascular mortality. Long-term fasting (LF) has been shown to improve plasma lipid profile. We performed an in-depth investigation of lipoprotein composition. METHODS: This observational study included 40 volunteers (50% men, aged 32-65 years), who underwent a medically supervised fast of 14 days (250 kcal/day). Changes in lipid and lipoprotein levels, as well as in lipoprotein subclasses and particles, were measured by ultracentrifugation and nuclear magnetic resonance (NMR) at baseline, and after 7 and 14 fasting days. RESULTS: The largest changes were found after 14 fasting days. There were significant reductions in triglycerides (TG, - 0.35 ± 0.1 mmol/L), very low-density lipoprotein (VLDL)-TG (- 0.46 ± 0.08 mmol/L), VLDL-cholesterol (VLDL-C, - 0.16 ± 0.03 mmol/L) and low-density lipoprotein (LDL)-C (- 0.72 ± 0.14 mmol/L). Analysis of LDL subclasses showed a significant decrease in LDL1-C (- 0.16 ± 0.05 mmol/L), LDL2-C (- 0.30 ± 0.06 mmol/L) and LDL3-C (- 0.27 ± 0.05 mmol/L). NMR spectroscopy showed a significant reduction in large VLDL particles (- 5.18 ± 1.26 nmol/L), as well as large (- 244.13 ± 39.45 nmol/L) and small LDL particles (- 38.45 ± 44.04 nmol/L). A significant decrease in high-density lipoprotein (HDL)-C (- 0.16 ± 0.04 mmol/L) was observed. By contrast, the concentration in large HDL particles was significantly raised. Apolipoprotein A1 decreased significantly whereas apolipoprotein B, lipoprotein(a), fibrinogen and high-sensitivity C-reactive protein were unchanged. CONCLUSION: Our results suggest that LF improves lipoprotein levels and lipoprotein subclasses and ameliorates the lipoprotein-associated atherogenic risk profile, suggesting a reduction in the cardiovascular risk linked to dyslipidemia. TRIAL REGISTRATION: Study registration number: DRKS-ID: DRKS00010111 Date of registration: 03/06/2016 "retrospectively registered".

Fasting-mediated metabolic and toxicity reprogramming impacts circulating microRNA levels in humans.

It is well-established that long-term fasting improves metabolic health, enhances the total antioxidant capacity and increases well-being. MicroRNAs oversee energy homeostasis and metabolic processes and are widely used as circulating biomarkers to identify the metabolic state. This study investigated whether the expression levels of twenty-four metabolism-associated microRNAs are significantly altered following long-term fasting and if these changes correlate with biochemical and redox parameters in the plasma. Thirty-two participants with an average BMI of 28 kg/m2 underwent a 10-day fasting period with a daily intake of 250 kcal under medical supervision. RT-qPCR on plasma small-RNA extracts revealed that the levels of seven microRNAs (miR-19b-3p, miR-22-3p, miR-122-5p, miR-126-3p, miR-142-3p, miR-143-3p, and miR-145-5p) were significantly altered following fasting. Importantly, the expression levels of these microRNAs have been consistently shown to change in the exact opposite direction in pathological states including obesity, diabetes, nonalcoholic steatohepatitis, and cardiovascular disease. Linear regression analyses revealed that among the microRNAs analyzed, anti-inflammatory miR-146-5p expression displayed most correlations with the levels of different biochemical and redox parameters. In silico analysis of fasting-associated microRNAs demonstrated that they target pathways that are highly enriched for intracellular signaling such mTOR, FoxO and autophagy, as well as extracellular matrix (ECM) interactions and cell-senescence. Overall, these data are consistent with a model in which long-term fasting engages homeostatic mechanisms associated with specific microRNAs to improve metabolic signaling regardless of health status.

Blood Pressure Changes in 1610 Subjects With and Without Antihypertensive Medication During Long-Term Fasting.

Background We investigated daily blood pressure (BP) changes during fasting periods ranging from 4 to 41 (10.0±3.8) days in a cohort of 1610 subjects, including 920 normotensive, 313 hypertensive nonmedicated, and 377 hypertensive medicated individuals. Methods and Results Subjects underwent a multidisciplinary fasting program with a daily intake of ≈250 kcal. Weight and stress scores decreased during fasting, and the well-being index increased, documenting a good tolerability. BP mean values decreased from 126.2±18.6/81.4±11.0 to 119.7±15.9/77.6±9.8 mm Hg (mean change, -6.5/3.8 mm Hg). BP changes were larger for hypertensive nonmedicated subjects (>140/90 mm Hg) and reduced by 16.7/8.8 mm Hg. This reduction reached 24.7/13.1 mm Hg for hypertensive nonmedicated subjects (n=76) with the highest BP (>160/100 mm Hg). In the normotensive group, BP decreased moderately by 3.0/1.9 mm Hg. Interestingly, we documented an increase of 6.3/2.2 mm Hg in a subgroup of 69 female subjects with BP <100/60 mm Hg. In the hypertensive medicated group, although BP decreased from 134.6/86.0 to 127.3/81.3 mm Hg, medication was stopped in 23.6% of the subjects, whereas dosage was reduced in 43.5% and remained unchanged in 19.4%. The decrease in BP was larger in subjects fasting longer. Baseline metabolic parameters, such as body mass index and glucose levels, as well as age, can be used to predict the amplitude of the BP decrease during fasting with a machine learning model. Conclusions Long-term fasting tends to decrease BP in subjects with elevated BP values. This effect persisted during the 4 days of stepwise food reintroduction, even when subjects stopped their antihypertensive medication. Registration URL: https://www.drks.de/drks_web/; Unique identifier: DRKS00010111.

Interplay between oxidative damage, the redox status, and metabolic biomarkers during long-term fasting.

Obesity and its related metabolic disorders, as well as infectious diseases like covid-19, are important health risks nowadays. It was recently documented that long-term fasting improves metabolic health and enhanced the total antioxidant capacity. The present study investigated the influence of a 10-day fasting on markers of the redox status in 109 subjects. Reducing power, 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation(ABTS) radical scavenging capacity, and hydroxyl radical scavenging capacity increased significantly, and indicated an increase of circulating antioxidant levels. No differences were detected in superoxide scavenging capacity, protein carbonyls, and superoxide dismutase when measured at baseline and after 10 days of fasting. These findings were concomitant to a decrease in blood glucose, insulin, glycated hemoglobin (HbA1c), total cholesterol, low-density lipoprotein (LDL) and triglycerides as well as an increase in total cholesterol/high-density lipoprotein (HDL) ratio. In addition, the well-being index as well as the subjective energy levels increased, documenting a good tolerability. There was an interplay between redox and metabolic parameters since lipid peroxidation baseline levels (thiobarbituric acid reactive substances [TBARS]) affected the ability of long-term fasting to normalize lipid levels. A machine learning model showed that a combination of antioxidant parameters measured at baseline predicted the efficiency of the fasting regimen to decrease LDL levels. In conclusion, it was demonstrated that long-term fasting enhanced the endogenous production of antioxidant molecules, that act protectively against free radicals, and in parallel improved the metabolic health status. Our results suggest that the outcome of long-term fasting strategies could be depending on the baseline values of the antioxidative and metabolic status of subjects.

Syntheses and Molecular Structures of Liquid Pyrophoric Hydridosilanes.

Trisilane, isotetrasilane, neopentasilane, and cyclohexasilane have been prepared in gram scale. In-situ cryo crystallization of these pyrophoric liquids in sealed capillaries on the diffractometer allows access to the single crystal structures of these compounds. Structural parameters are discussed and compared to gas-phase electron diffraction structures from literature and with the results from quantum chemical calculations. Significantly higher packing indices are found for the silanes compared to the corresponding alkanes. Radiation with ultraviolet light (365 nm) and parallel ESR (EPR) measurement shows that cyclohexasilane is easily split into radicals, which subsequently leads to the formation of branched and chain-like oligomers. The other compounds form no radicals under these conditions. NMR spectra of all four compounds have been recorded.

Influence of Long-Term Fasting on Blood Redox Status in Humans.

Fasting is increasingly practiced to improve health and general well-being, as well as for its cytoprotective effects. Changes in blood redox status, linked to the development of a variety of metabolic diseases, have been recently documented during calorie restriction and intermittent fasting, but not with long-term fasting (LF). We investigated some parameters of the blood redox profile in 109 subjects before and after a 10-day fasting period. Fasting resulted in a significant reduction in body weight, improved well-being and had a beneficial modulating effect on blood lipids and glucose regulation. We observed that fasting decreased lipid peroxidation (TBARS) and increased total antioxidant capacity (TAC) in plasma, concomitant with a uric acid elevation, known to be associated with fasting and did not cause gout attacks. Reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx) and catalase in erythrocytes did not show significant changes. In addition, reduction in body weight, waist circumference, and glucose levels were associated to a reduced lipid peroxidation. Similar results were obtained by grouping subjects on the basis of the changes in their GSH levels, showing that a period of 10 days fasting improves blood redox status regardless of GSH status in the blood.

Unravelling the health effects of fasting: a long road from obesity treatment to healthy life span increase and improved cognition.

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-MESSAGESBiochemical 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.Ketones reduce appetite and help maintain effective fasting.Application of fasting patterns increases healthy life span and defences against oxidative and metabolic stresses.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.Long-term fasting, with durations between 5 and 21 days can be successfully repeated in the course of a year.

Changes in human gut microbiota composition are linked to the energy metabolic switch during 10 d of Buchinger fasting.

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.

Effects of Periodic Fasting on Fatty Liver Index-A Prospective Observational Study.

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.

Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects.

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.