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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
62
the participants will undergo a fasting program that includes the daily intake of 250 kcal under medical supervision
Buchinger Wilhelmi clinic
Überlingen, Germany
Changes in whole body composition
Fat mass, lean mass, water content measured by magnetic resonance imaging
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards
Changes in the composition of the adipose tissue
Fat mass, lean mass, water content measured by magnetic resonance imaging
Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards
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Changes in HDL cholesterol efflux capacity
measured in serum by a standardized used radioisotopic technique
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards
Changes in brain morphometry
measured by magnetic resonance imaging
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards
Changes in GlycA
determined in serum
Time frame: 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
Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards
Changes in chylomicrons
determined in serum
Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards
Changes in oxidized phospholipids
determined in serum
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards