Long-term Fasting: Multi-system Adaptations in Humans
- Conditions
- Fasting
- Interventions
- Other: Long-term fasting according to the Buchinger Wilhelmi fasting program
- Registration Number
- NCT05031598
- Lead Sponsor
- Buchinger Wilhelmi Development & Holding GmbH
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 62
- BMI between 22 - 35 kg/m2
- intake of medication (cardiovascular diseases, lipid and glucose metabolism)
- chronic manifest psychical and psychiatric diseases
- participation in another study
- pregnancy or breastfeeding
- in the MRI/MRS sub-study, any MRI contraindication (claustrophobia, pacemakers, MR-incompatible prosthetic valves, metallic implants, foreign metallic body)
- active uncontrolled gastrointestinal disorders including ulcerative colitis, Crohn's disease, indeterminate colitis, severe irritable bowel syndrome, persistent infectious gastroenteritis, persistent or chronic diarrhea of unknown etiology, recurrent Clostridium difficile infection
- major surgery of the GI tract, in the past five years. Any major bowel resection at any time
- intake of antibiotics in the last 2 months
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Long-term fasting Long-term fasting according to the Buchinger Wilhelmi fasting program The participants will undergo 6-12 fasting days according to the Buchinger Wilhelmi fasting program
- Primary Outcome Measures
Name Time Method Changes in the composition of the quadriceps Baseline and changes at the end of fasting as well as one and four months afterwards Fat mass, lean mass, water content measured by magnetic resonance imaging
Changes in HDL cholesterol efflux capacity Baseline and changes at the end of fasting as well as one and four months afterwards measured in serum by a standardized used radioisotopic technique
Changes in the composition of the heart Baseline and changes at the end of fasting as well as one and four months afterwards Fat mass, lean mass, water content measured by magnetic resonance imaging
Changes in the composition of the kidney Baseline and changes at the end of fasting as well as one and four months afterwards Fat mass, lean mass, water content measured by magnetic resonance imaging
Changes in HS-Omega-3 Index Baseline and changes at the end of fasting as well as one and four months afterwards 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
Changes in faecal microbiota composition and function (carbohydrate metabolism) Baseline and changes after an average of 10 (+/-3) fasting days Shotgun metagenomics, 5Gb of DNA sequencing data.
Changes in the composition of the spleen Baseline and changes at the end of fasting as well as one and four months afterwards Fat mass, lean mass, water content measured by magnetic resonance imaging
Changes in the composition of the adipose tissue Baseline and changes at the end of fasting as well as one and four months afterwards Fat mass, lean mass, water content measured by magnetic resonance imaging
Changes in serum cholesterol loading capacity Baseline and changes at the end of fasting as well as one and four months afterwards measured in serum using radioactive cholesterol loaded macrophages
Changes in whole body composition Baseline and changes at the end of fasting as well as one and four months afterwards Fat mass, lean mass, water content measured by magnetic resonance imaging
Changes in the composition of the liver Baseline and changes at the end of fasting as well as one and four months afterwards Fat mass, lean mass, water content measured by magnetic resonance imaging
Changes in metabolome Baseline and changes after 3 fasting days, the end of fasting as well as one and four months afterwards 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
Changes in hydrogen sulfide production capacity Baseline and changes at the end of fasting as well as one and four months afterwards measured in serum and urine using the lead acetate assay
- Secondary Outcome Measures
Name Time Method Changes in persulfidation Baseline, and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards persulfidation in serum and urine
Changes in GlycA Baseline and changes at the end of fasting as well as one and four months afterwards determined in serum
Changes in mean diffusivity (MD) Baseline and changes at the end of fasting as well as one and four months afterwards measured with magnetic impedance imaging
Changes in cardiovascular fitness Baseline and changes at the end of fasting as well as one and four months afterwards using the maximal oxygen consumption (VO2max)
Changes in muscle metabolism and mitochondrial oxidative capacity: TauPCr(s) Baseline and changes at the end of fasting as well as one and four months afterwards during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy)
Changes in muscle metabolism and mitochondrial oxidative capacity: ATP concentration Baseline and changes at the end of fasting as well as one and four months afterwards during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy)
Changes in muscle metabolism and mitochondrial oxidative capacity: T1 of metabolites at rest Baseline and changes at the end of fasting as well as one and four months afterwards during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy)
Changes in fiber strain (Eff) Baseline and changes at the end of fasting as well as one and four months afterwards measured with magnetic impedance imaging
Changes in fractional anisotropy (FA) Baseline and changes at the end of fasting as well as one and four months afterwards measured with magnetic impedance imaging
Changes in systolic cardiac function Baseline and changes at the end of fasting as well as one and four months afterwards 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
Changes in apparent diffusion coefficient (ADC) Baseline and changes at the end of fasting as well as one and four months afterwards measured with magnetic impedance imaging
Changes in muscle metabolism and mitochondrial oxidative capacity: PCr hydrolysis (%) Baseline and changes at the end of fasting as well as one and four months afterwards during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy)
Changes in multiparametric muscle quantification: T2 Baseline and changes at the end of fasting as well as one and four months afterwards measured with quantitative magnetic impedance imaging
Changes in multiparametric muscle quantification: T2 * relaxation time Baseline and changes at the end of fasting as well as one and four months afterwards measured with quantitative magnetic impedance imaging
Changes in brain morphometry Baseline and changes at the end of fasting as well as one and four months afterwards measured by magnetic resonance imaging
Changes in cardiac mass Baseline and changes at the end of fasting as well as one and four months afterwards measured by magnetic resonance imaging
Changes in lower limbs (quadriceps, hamstrings, calves) Baseline and changes at the end of fasting as well as one and four months afterwards measured by magnetic resonance imaging
Changes in diastolic cardiac function Baseline and changes at the end of fasting as well as one and four months afterwards global and regional diastolic function (peak filling rate, torsion rate, diastolic strain rate) measured with magnetic resonance imaging
Changes in muscle metabolism and mitochondrial oxidative capacity: PCr concentration Baseline and changes at the end of fasting as well as one and four months afterwards during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy)
Changes in muscle metabolism and mitochondrial oxidative capacity: Pi concentration Baseline and changes at the end of fasting as well as one and four months afterwards during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy)
Changes in oxidized phospholipids Baseline and changes at the end of fasting as well as one and four months afterwards determined in serum
Changes in enzymes Baseline and changes after 3 fasting days, the end of fasting as well as one and four months afterwards immunoblotting of relevantly altered enzymes in PBMCs
Changes in lumbosacral muscle mass Baseline and changes at the end of fasting as well as one and four months afterwards measured by magnetic resonance imaging
Changes in helix angle (HA) Baseline and changes at the end of fasting as well as one and four months afterwards measured with magnetic impedance imaging
Changes in paraoxonase (PON-1) activity Baseline and changes at the end of fasting as well as one and four months afterwards determined in serum
Changes in proprotein convertase subtilisin/kexin type 9 (PCSK9) Baseline and changes at the end of fasting as well as one and four months afterwards determined in serum by ELISA
Changes in muscle metabolism and mitochondrial oxidative capacity: pH at rest and post exercise in mM Baseline and changes at the end of fasting as well as one and four months afterwards during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy)
Changes in muscle metabolism and mitochondrial oxidative capacity: PCr consumption Baseline and changes at the end of fasting as well as one and four months afterwards during ergometric effort in MRI at the level of the sural muscle (31P spectroscopy)
Changes in sulfur compounds Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards 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
Changes in multiparametric muscle quantification: susceptibility (chi) Baseline and changes at the end of fasting as well as one and four months afterwards measured with quantitative magnetic impedance imaging
Changes in DNA methylation Baseline and changes at the end of fasting as well as one and four months afterwards biomarker of biological aging using erythrocytes
Changes in serum amyloid A levels Baseline and changes at the end of fasting as well as one and four months afterwards determined in serum
Changes in lipoprotein transfer enzymes Baseline and changes at the end of fasting as well as one and four months afterwards CETP activity, determined as U/ml using a commercially available assay
Changes in chylomicrons Baseline and changes at the end of fasting as well as one and four months afterwards determined in serum
Changes in multiparametric muscle quantification: fat fraction (PDFF) Baseline and changes at the end of fasting as well as one and four months afterwards measured with quantitative magnetic impedance imaging
Changes in quadricipital maximum voluntary contraction Baseline and changes at the end of fasting as well as one and four months afterwards measured with magnetic impedance imaging
Changes in thiosulfate levels Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards measured using the monobromobimane method using HPLC and LC-MS/MS
Changes in cysteine and cystine levels Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards 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
Changes in amino acids Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards using a targeted approach in serum and urine
Trial Locations
- Locations (1)
Buchinger Wilhelmi clinic
🇩🇪Überlingen, Germany