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| Name | Class |
|---|---|
| Buchinger Wilhelmi Clinic | UNKNOWN |
| Claude Bernard University | OTHER |
| University of Milan | OTHER |
| Omegametrix GmbH |
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The aim of this trial is to investigate the effects of long-term fasting on size, mass, composition and function of metabolic active tissues in several organs that reexpand possibly rejuvenated after 1-4 months. Additionally, the lipid metabolism is investigated in depth.
Fasting displays numerous positive effects on metabolism, health and aging. Surprisingly, few considerations are given to long-term fasting periods.
The metabolic switch from food-derived glucose to adipose tissue-derived fatty acids and ketones as primary cellular fuel is the key to fasting metabolism. Fasting has been shown to improve cardiovascular risk factors and gut microbiota in humans. It provokes profound changes in lipid metabolism. However, many questions are still open concerning the mobilization, exchange, and function of lipids during long-term fasting. Furthermore, recent results show the ability of periodic restrictive nutritional strategies to trigger organ regeneration. This promising regenerative power has not been investigated comprehensively in humans. In addition, the knowledge about the role of human faecal microbiota in health and disease is increasing. Only little is known about its composition and function during fasting. We found indications that the gut microbiome could influence energy metabolism and consequently could influence the dynamic of the metabolic switch.
Long-term fasting under medical supervision according to the Buchinger Wilhelmi fasting program has been demonstrated to be safe and well-tolerated.
The current project investigates the effects of a 9±3 days fasting period by a multi-systemic approach focusing on lipid metabolism and the gut microbiome in 100 subjects. Additionally, the body composition in combination with muscle performance will be analyzed in-depth in a subgroup of 32 subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Long-term fasting | Experimental | The participants will undergo 6-12 fasting days according to the Buchinger Wilhelmi fasting program |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Long-term fasting according to the Buchinger Wilhelmi fasting program | Other | the participants will undergo a fasting program that includes the daily intake of 250 kcal under medical supervision |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in whole body composition | Fat mass, lean mass, water content measured by magnetic resonance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in the composition of the heart | Fat mass, lean mass, water content measured by magnetic resonance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in the composition of the liver | Fat mass, lean mass, water content measured by magnetic resonance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in the composition of the kidney | Fat mass, lean mass, water content measured by magnetic resonance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in the composition of the spleen | Fat mass, lean mass, water content measured by magnetic resonance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in the composition of the quadriceps | Fat mass, lean mass, water content measured by magnetic resonance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in the composition of the adipose tissue |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in brain morphometry | measured by magnetic resonance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in cardiac mass | measured by magnetic resonance imaging |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in body weight | in kg | Baseline, daily during fasting and food reintroduction as well as one and four months afterwards |
| Changes in body mass index | in kg/m² |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Françoise Wilhelmi de Toledo, Dr | Buchinger Wilhelmi Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Buchinger Wilhelmi clinic | Überlingen | 88662 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39180960 | Derived | Grundler F, Palumbo M, Adorni MP, Zimetti F, Papotti B, Plonne D, Holley A, Mesnage R, Ruscica M, Wilhelmi de Toledo F. HDL cholesterol efflux capacity and cholesterol loading capacity in long-term fasting: Evidence from a prospective, single-arm interventional study in healthy individuals. Atherosclerosis. 2024 Oct;397:118548. doi: 10.1016/j.atherosclerosis.2024.118548. Epub 2024 Aug 6. | |
| 36466423 |
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| ID | Term |
|---|---|
| D005215 | Fasting |
| ID | Term |
|---|---|
| D005247 | Feeding Behavior |
| D001519 | Behavior |
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| UNKNOWN |
| King's College London | OTHER |
| MVZ Humangenetik Ulm | UNKNOWN |
| University of Graz | OTHER |
| Leiden University Medical Center | OTHER |
| MVZ Labor Ravensburg | UNKNOWN |
| ETH Zurich | OTHER |
single-arm interventional study
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Fat mass, lean mass, water content measured by magnetic resonance imaging
| Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in HDL cholesterol efflux capacity | measured in serum by a standardized used radioisotopic technique | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in serum cholesterol loading capacity | measured in serum using radioactive cholesterol loaded macrophages | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in HS-Omega-3 Index | Determination of fatty acid (C 14:0; 16:0; 18:0; 20:0; 22:0; 24:0; 16:1 n-7; 18:1 n-9; 20:1 n-9; 24:1 n-9; 18:2 n-6; 18: 3 n-6; 20: 3 n-6; 22:2 n-6; 20:4 n-6; 22:4 n-6; 22:5 n-6; 18: 3 n-3; 20:5 n-3; 22:5 n-3; 22:6 n-3; 16:1 n-7t; 18:1 n-9t; 18:2 n-6tt; 18:2 n-6ct; 18:2 n-6tc) in erythrocyte membranes with highly standardized analytical procedure | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in faecal microbiota composition and function (carbohydrate metabolism) | Shotgun metagenomics, 5Gb of DNA sequencing data. | Baseline and changes after an average of 10 (+/-3) fasting days |
| Changes in metabolome | using an untargeted metabolomics approach to investigate changes in the metabolome, with a focus on the polyamine biosynthetic pathway at the cellular level in PBMCs and compare them with changes in the circulating plasma/serum metabolome | Baseline and changes after 3 fasting days, the end of fasting as well as one and four months afterwards |
| Changes in hydrogen sulfide production capacity | measured in serum and urine using the lead acetate assay | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in lower limbs (quadriceps, hamstrings, calves) | measured by magnetic resonance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in lumbosacral muscle mass | measured by magnetic resonance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in systolic cardiac function | global and regional function (right and left ejection fraction, right and left end-diastolic and end-systolic volumes, peak regional strains (circumferential, longitudinal strain) measured with magnetic resonance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in diastolic cardiac function | global and regional diastolic function (peak filling rate, torsion rate, diastolic strain rate) measured with magnetic resonance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in apparent diffusion coefficient (ADC) | measured with magnetic impedance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in fiber strain (Eff) | measured with magnetic impedance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in fractional anisotropy (FA) | measured with magnetic impedance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in helix angle (HA) | measured with magnetic impedance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in mean diffusivity (MD) | measured with magnetic impedance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in cardiovascular fitness | using the maximal oxygen consumption (VO2max) | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in muscle metabolism and mitochondrial oxidative capacity: TauPCr(s) | during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy) | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in muscle metabolism and mitochondrial oxidative capacity: PCr hydrolysis (%) | during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy) | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in muscle metabolism and mitochondrial oxidative capacity: PCr concentration | during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy) | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in muscle metabolism and mitochondrial oxidative capacity: Pi concentration | during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy) | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in muscle metabolism and mitochondrial oxidative capacity: ATP concentration | during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy) | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in muscle metabolism and mitochondrial oxidative capacity: pH at rest and post exercise in mM | during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy) | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in muscle metabolism and mitochondrial oxidative capacity: T1 of metabolites at rest | during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy) | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in muscle metabolism and mitochondrial oxidative capacity: PCr consumption | during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy) | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in multiparametric muscle quantification: T2 | measured with quantitative magnetic impedance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in multiparametric muscle quantification: T2 * relaxation time | measured with quantitative magnetic impedance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in multiparametric muscle quantification: susceptibility (chi) | measured with quantitative magnetic impedance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in multiparametric muscle quantification: fat fraction (PDFF) | measured with quantitative magnetic impedance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in quadricipital maximum voluntary contraction | measured with magnetic impedance imaging | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in DNA methylation | biomarker of biological aging using erythrocytes | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in serum amyloid A levels | determined in serum | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in paraoxonase (PON-1) activity | determined in serum | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in lipoprotein transfer enzymes | CETP activity, determined as U/ml using a commercially available assay | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in GlycA | determined in serum | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in proprotein convertase subtilisin/kexin type 9 (PCSK9) | determined in serum by ELISA | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in chylomicrons | determined in serum | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in oxidized phospholipids | determined in serum | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in enzymes | immunoblotting of relevantly altered enzymes in PBMCs | Baseline and changes after 3 fasting days, the end of fasting as well as one and four months afterwards |
| Changes in persulfidation | persulfidation in serum and urine | Baseline, and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards |
| Changes in sulfur compounds | amino acids (using a targeted approach), thiosulfate (measured using the monobromobimane method using HPLC and LC-MS/MS), cysteine and cystine (use the S-sulfocysteine (SSC) method which is a HPLC-based method using automated precolumn derivatization with OPA and UV detection at 338 nm) in serum and urine | Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards |
| Changes in thiosulfate levels | measured using the monobromobimane method using HPLC and LC-MS/MS | Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards |
| Changes in cysteine and cystine levels | using the S-sulfocysteine (SSC) method which is a HPLC-based method using automated precolumn derivatization with OPA and UV detection at 338 nm in serum and urine | Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards |
| Changes in amino acids | using a targeted approach in serum and urine | Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards |
| Baseline, daily during fasting and food reintroduction as well as one and four months afterwards |
| Changes in abdominal circumference | in cm | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in resting systolic blood pressure | in mmHg | Baseline, daily during fasting and food reintroduction as well as one and four months afterwards |
| Changes in resting diastolic blood pressure | in mmHg | Baseline, daily during fasting and food reintroduction as well as one and four months afterwards |
| Changes in resting heart frequency | in beats/min | Baseline, daily during fasting and food reintroduction as well as one and four months afterwards |
| Changes in bio-electrical multifrequency impedance analysis | Global and segmental body composition (water, fat and lean mass), liquid distribution (total, extracellular and intracellular water), metabolic indexes (metabolic activity index (MAI), protein content (total and active cell mass fraction) as determined by bioimpedance analysis | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in liver stiffness | measured by FibroScan | Baseline, during and after fasting |
| Changes in physical activity | intensity, duration, frequency measured by triaxial actigraphy | Before, daily during fasting as well as one and four months afterwards |
| Changes in circadian rhythm and sleep | measured by triaxial actigraphy | Before, daily during fasting as well as one and four months afterwards |
| Changes in mental well-being | questionnaires: Warwick-Edinburgh Mental Well-Being Scale | Baseline and at the end of fasting as well as one and four months afterwards |
| Changes in global health | questionnaires: PROMIS Scale | Baseline and at the end of fasting as well as one and four months afterwards |
| Changes in physical activity | questionnaires: Godin Leisure-Time Exercise Questionnaire | Baseline and at the end of fasting as well as one and four months afterwards |
| Changes in sleep quality | questionnaires: Pittsburgh Sleep Quality Index | Baseline and at the end of fasting as well as one and four months afterwards |
| Changes in ketonuria | Ketone bodies in urine measured by urine dip sticks | during the fasting period and food reintroduction |
| Changes in ketonemia | Ketone bodies in capillary blood | during the fasting period and food reintroduction |
| Changes in glycemia | Glucose in capillary blood | during the fasting period and food reintroduction |
| Changes in dietary behaviour | questionnaire: short healthy eating index survey | Baseline and after fasting as well as one and four months afterwards |
| Changes in smoking behaviour | questionnaire | Baseline and after fasting as well as one and four months afterwards |
| Changes in alcohol consumption | questionnaire | Baseline and after fasting as well as one and four months afterwards |
| Changes in physical activity | in hours/week | Baseline and after fasting as well as one and four months afterwards |
| Changes in energy level | measured by visual scale (0-10) | Baseline, daily during fasting and food reintroduction as well as one and four months afterwards |
| Changes in emotional well-being | measured by visual scale (0-10) | Baseline, daily during fasting and food reintroduction as well as one and four months afterwards |
| Changes in physical well-being | measured by visual scale (0-10) | Baseline, daily during fasting and food reintroduction as well as one and four months afterwards |
| Changes in symptoms: fatigue | measured by visual scale (0-10) | Baseline, daily during fasting and food reintroduction as well as one and four months afterwards |
| Changes in symptoms: muscle weakness | measured by visual scale (0-10) | Baseline, daily during fasting and food reintroduction as well as one and four months afterwards |
| Changes in symptoms: back pain | measured by visual scale (0-10) | Baseline, daily during fasting and food reintroduction as well as one and four months afterwards |
| Changes in symptoms: hunger | measured by visual scale (0-10) | Baseline, daily during fasting and food reintroduction as well as one and four months afterwards |
| Changes in symptoms: anxiety | measured by visual scale (0-10) | Baseline, daily during fasting and food reintroduction as well as one and four months afterwards |
| Changes in symptoms: headache | measured by visual scale (0-10) | Baseline, daily during fasting and food reintroduction as well as one and four months afterwards |
| Changes in symptoms: sleep disturbances | measured by visual scale (0-10) | Baseline, daily during fasting and food reintroduction as well as one and four months afterwards |
| Adverse events | Documentation of side effects | through study completion, an average of 4.5 months |
| Changes in blood count | blood parameters: leucocytes, erythrocytes, haemoglobin, haematocrit, MCV, MCH, MCHC, thrombocytes, bilirubin | Baseline and at the end of fasting as well as one and four months afterwards |
| Changes in differential blood count | blood parameters: basophiles, neutrophils, eosinophiles, monocytes, reticulocytes | Baseline and at the end of fasting as well as one and four months afterwards |
| Changes in coagulation | blood parameters: INR, PTT in sec | Baseline and at the end of fasting as well as one and four months afterwards |
| Changes in liver enzymes | blood parameters: GOT, GPT, GGT, AP in U/l | Baseline and at the end of fasting as well as one and four months afterwards |
| Changes in kidney parameters | blood parameters: uric acid, urea, creatinine in mg/dl | Baseline and at the end of fasting as well as one and four months afterwards |
| Changes in inflammatory parameters | blood parameters: hs-CRP, ESR in mm/h, inflammasome, cortisol in µg/dl | Baseline and at the end of fasting as well as one and four months afterwards |
| Changes in glucose metabolism | blood parameters: glucose in mmol/l, HbA1c in %, insulin in mU/l | Baseline and at the end of fasting as well as one and four months afterwards |
| Changes in lipid parameters | blood parameters: total cholesterol, HDL-C, LDL-C, triglycerides in mmol/l | Baseline and at the end of fasting as well as one and four months afterwards |
| Changes in electrolytes | blood parameters: sodium, potassium, calcium, magnesium in mmol/l | Baseline and at the end of fasting as well as one and four months afterwards |
| Changes in the immune response to fasting | using single cell nucleus sequencing | Baseline, after 3 fasting days, and at the end of fasting as well as one and four months afterwards |
| Changes in cell populations (natural killer and T cells) | using single cell nucleus sequencing | Baseline, after 3 fasting days, and at the end of fasting as well as one and four months afterwards |
| Changes in lipoprotein subclasses | determined in serum by high-density ultracentrifugation reflecting cholesterol and triglyceride composition | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in apolipoproteins | ApoA-I and ApoB determined in serum | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in lipoprotein(a) | determined in serum | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Changes in methylation based clocks | biomarker of biological aging using PBMCs | Baseline and changes at the end of fasting as well as one and four months afterwards |
| Sociodemographic Measurements | Age, gender, language, complete family history, current and previous illness and co-morbidities, and current medications | Baseline |
| Changes in nitrogen balance | nitrogen in 24-hours-urine | Baseline, daily during fasting as well as food reintroduction |
| Derived |
| Grundler F, Viallon M, Mesnage R, Ruscica M, von Schacky C, Madeo F, Hofer SJ, Mitchell SJ, Croisille P, Wilhelmi de Toledo F. Long-term fasting: Multi-system adaptations in humans (GENESIS) study-A single-arm interventional trial. Front Nutr. 2022 Nov 17;9:951000. doi: 10.3389/fnut.2022.951000. eCollection 2022. |