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OpenTrials
Completed

NCT Number: NCT05031598

Long-term Fasting: Multi-system Adaptations in Humans

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.

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Key information

Conditions

Fasting Behavior Feeding Behavior

Age range

20 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Buchinger Wilhelmi clinic

Überlingen, 88662, Germany

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • BMI between 22 - 35 kg/m2

Exclusion criteria

  • 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

Treatment and study plan

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

Primary outcomes

  1. Changes in whole body composition

    Time frame: 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

  2. Changes in the composition of the heart

    Time frame: 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

  3. Changes in the composition of the liver

    Time frame: 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

  4. Changes in the composition of the kidney

    Time frame: 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

  5. Changes in the composition of the spleen

    Time frame: 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

  6. Changes in the composition of the quadriceps

    Time frame: 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

  7. Changes in the composition of the adipose tissue

    Time frame: 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

  8. Changes in HDL cholesterol efflux capacity

    Time frame: 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

  9. Changes in serum cholesterol loading capacity

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    measured in serum using radioactive cholesterol loaded macrophages

  10. Changes in HS-Omega-3 Index

    Time frame: 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

  11. Changes in faecal microbiota composition and function (carbohydrate metabolism)

    Time frame: Baseline and changes after an average of 10 (+/-3) fasting days

    Shotgun metagenomics, 5Gb of DNA sequencing data.

  12. Changes in metabolome

    Time frame: 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

  13. Changes in hydrogen sulfide production capacity

    Time frame: 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 outcomes

  1. Changes in brain morphometry

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    measured by magnetic resonance imaging

  2. Changes in cardiac mass

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    measured by magnetic resonance imaging

  3. Changes in lower limbs (quadriceps, hamstrings, calves)

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    measured by magnetic resonance imaging

  4. Changes in lumbosacral muscle mass

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    measured by magnetic resonance imaging

  5. Changes in systolic cardiac function

    Time frame: 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

  6. Changes in diastolic cardiac function

    Time frame: 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

  7. Changes in apparent diffusion coefficient (ADC)

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    measured with magnetic impedance imaging

  8. Changes in fiber strain (Eff)

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    measured with magnetic impedance imaging

  9. Changes in fractional anisotropy (FA)

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    measured with magnetic impedance imaging

  10. Changes in helix angle (HA)

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    measured with magnetic impedance imaging

  11. Changes in mean diffusivity (MD)

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    measured with magnetic impedance imaging

  12. Changes in cardiovascular fitness

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    using the maximal oxygen consumption (VO2max)

  13. Changes in muscle metabolism and mitochondrial oxidative capacity: TauPCr(s)

    Time frame: 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)

  14. Changes in muscle metabolism and mitochondrial oxidative capacity: PCr hydrolysis (%)

    Time frame: 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)

  15. Changes in muscle metabolism and mitochondrial oxidative capacity: PCr concentration

    Time frame: 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)

  16. Changes in muscle metabolism and mitochondrial oxidative capacity: Pi concentration

    Time frame: 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)

  17. Changes in muscle metabolism and mitochondrial oxidative capacity: ATP concentration

    Time frame: 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)

  18. Changes in muscle metabolism and mitochondrial oxidative capacity: pH at rest and post exercise in mM

    Time frame: 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)

  19. Changes in muscle metabolism and mitochondrial oxidative capacity: T1 of metabolites at rest

    Time frame: 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)

  20. Changes in muscle metabolism and mitochondrial oxidative capacity: PCr consumption

    Time frame: 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)

  21. Changes in multiparametric muscle quantification: T2

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    measured with quantitative magnetic impedance imaging

  22. Changes in multiparametric muscle quantification: T2 * relaxation time

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    measured with quantitative magnetic impedance imaging

  23. Changes in multiparametric muscle quantification: susceptibility (chi)

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    measured with quantitative magnetic impedance imaging

  24. Changes in multiparametric muscle quantification: fat fraction (PDFF)

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    measured with quantitative magnetic impedance imaging

  25. Changes in quadricipital maximum voluntary contraction

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    measured with magnetic impedance imaging

  26. Changes in DNA methylation

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    biomarker of biological aging using erythrocytes

  27. Changes in serum amyloid A levels

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    determined in serum

  28. Changes in paraoxonase (PON-1) activity

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    determined in serum

  29. Changes in lipoprotein transfer enzymes

    Time frame: 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

  30. Changes in GlycA

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    determined in serum

  31. Changes in proprotein convertase subtilisin/kexin type 9 (PCSK9)

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    determined in serum by ELISA

  32. Changes in chylomicrons

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    determined in serum

  33. Changes in oxidized phospholipids

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    determined in serum

  34. Changes in enzymes

    Time frame: 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

  35. Changes in persulfidation

    Time frame: 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

  36. Changes in sulfur compounds

    Time frame: 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

  37. Changes in thiosulfate levels

    Time frame: 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

  38. Changes in cysteine and cystine levels

    Time frame: 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

  39. Changes in amino acids

    Time frame: 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

Other outcomes

  1. Changes in body weight

    Time frame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards

    in kg

  2. Changes in body mass index

    Time frame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards

    in kg/m²

  3. Changes in abdominal circumference

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    in cm

  4. Changes in resting systolic blood pressure

    Time frame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards

    in mmHg

  5. Changes in resting diastolic blood pressure

    Time frame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards

    in mmHg

  6. Changes in resting heart frequency

    Time frame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards

    in beats/min

  7. Changes in bio-electrical multifrequency impedance analysis

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    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

  8. Changes in liver stiffness

    Time frame: Baseline, during and after fasting

    measured by FibroScan

  9. Changes in physical activity

    Time frame: Before, daily during fasting as well as one and four months afterwards

    intensity, duration, frequency measured by triaxial actigraphy

  10. Changes in circadian rhythm and sleep

    Time frame: Before, daily during fasting as well as one and four months afterwards

    measured by triaxial actigraphy

  11. Changes in mental well-being

    Time frame: Baseline and at the end of fasting as well as one and four months afterwards

    questionnaires: Warwick-Edinburgh Mental Well-Being Scale

  12. Changes in global health

    Time frame: Baseline and at the end of fasting as well as one and four months afterwards

    questionnaires: PROMIS Scale

  13. Changes in physical activity

    Time frame: Baseline and at the end of fasting as well as one and four months afterwards

    questionnaires: Godin Leisure-Time Exercise Questionnaire

  14. Changes in sleep quality

    Time frame: Baseline and at the end of fasting as well as one and four months afterwards

    questionnaires: Pittsburgh Sleep Quality Index

  15. Changes in ketonuria

    Time frame: during the fasting period and food reintroduction

    Ketone bodies in urine measured by urine dip sticks

  16. Changes in ketonemia

    Time frame: during the fasting period and food reintroduction

    Ketone bodies in capillary blood

  17. Changes in glycemia

    Time frame: during the fasting period and food reintroduction

    Glucose in capillary blood

  18. Changes in dietary behaviour

    Time frame: Baseline and after fasting as well as one and four months afterwards

    questionnaire: short healthy eating index survey

  19. Changes in smoking behaviour

    Time frame: Baseline and after fasting as well as one and four months afterwards

    questionnaire

  20. Changes in alcohol consumption

    Time frame: Baseline and after fasting as well as one and four months afterwards

    questionnaire

  21. Changes in physical activity

    Time frame: Baseline and after fasting as well as one and four months afterwards

    in hours/week

  22. Changes in energy level

    Time frame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards

    measured by visual scale (0-10)

  23. Changes in emotional well-being

    Time frame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards

    measured by visual scale (0-10)

  24. Changes in physical well-being

    Time frame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards

    measured by visual scale (0-10)

  25. Changes in symptoms: fatigue

    Time frame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards

    measured by visual scale (0-10)

  26. Changes in symptoms: muscle weakness

    Time frame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards

    measured by visual scale (0-10)

  27. Changes in symptoms: back pain

    Time frame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards

    measured by visual scale (0-10)

  28. Changes in symptoms: hunger

    Time frame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards

    measured by visual scale (0-10)

  29. Changes in symptoms: anxiety

    Time frame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards

    measured by visual scale (0-10)

  30. Changes in symptoms: headache

    Time frame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards

    measured by visual scale (0-10)

  31. Changes in symptoms: sleep disturbances

    Time frame: Baseline, daily during fasting and food reintroduction as well as one and four months afterwards

    measured by visual scale (0-10)

  32. Adverse events

    Time frame: through study completion, an average of 4.5 months

    Documentation of side effects

  33. Changes in blood count

    Time frame: Baseline and at the end of fasting as well as one and four months afterwards

    blood parameters: leucocytes, erythrocytes, haemoglobin, haematocrit, MCV, MCH, MCHC, thrombocytes, bilirubin

  34. Changes in differential blood count

    Time frame: Baseline and at the end of fasting as well as one and four months afterwards

    blood parameters: basophiles, neutrophils, eosinophiles, monocytes, reticulocytes

  35. Changes in coagulation

    Time frame: Baseline and at the end of fasting as well as one and four months afterwards

    blood parameters: INR, PTT in sec

  36. Changes in liver enzymes

    Time frame: Baseline and at the end of fasting as well as one and four months afterwards

    blood parameters: GOT, GPT, GGT, AP in U/l

  37. Changes in kidney parameters

    Time frame: Baseline and at the end of fasting as well as one and four months afterwards

    blood parameters: uric acid, urea, creatinine in mg/dl

  38. Changes in inflammatory parameters

    Time frame: Baseline and at the end of fasting as well as one and four months afterwards

    blood parameters: hs-CRP, ESR in mm/h, inflammasome, cortisol in µg/dl

  39. Changes in glucose metabolism

    Time frame: Baseline and at the end of fasting as well as one and four months afterwards

    blood parameters: glucose in mmol/l, HbA1c in %, insulin in mU/l

  40. Changes in lipid parameters

    Time frame: Baseline and at the end of fasting as well as one and four months afterwards

    blood parameters: total cholesterol, HDL-C, LDL-C, triglycerides in mmol/l

  41. Changes in electrolytes

    Time frame: Baseline and at the end of fasting as well as one and four months afterwards

    blood parameters: sodium, potassium, calcium, magnesium in mmol/l

  42. Changes in the immune response to fasting

    Time frame: Baseline, after 3 fasting days, and at the end of fasting as well as one and four months afterwards

    using single cell nucleus sequencing

  43. Changes in cell populations (natural killer and T cells)

    Time frame: Baseline, after 3 fasting days, and at the end of fasting as well as one and four months afterwards

    using single cell nucleus sequencing

  44. Changes in lipoprotein subclasses

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    determined in serum by high-density ultracentrifugation reflecting cholesterol and triglyceride composition

  45. Changes in apolipoproteins

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    ApoA-I and ApoB determined in serum

  46. Changes in lipoprotein(a)

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    determined in serum

  47. Changes in methylation based clocks

    Time frame: Baseline and changes at the end of fasting as well as one and four months afterwards

    biomarker of biological aging using PBMCs

  48. Sociodemographic Measurements

    Time frame: Baseline

    Age, gender, language, complete family history, current and previous illness and co-morbidities, and current medications

  49. Changes in nitrogen balance

    Time frame: Baseline, daily during fasting as well as food reintroduction

    nitrogen in 24-hours-urine

Sponsors and collaborators

Lead sponsor

Buchinger Wilhelmi Development & Holding GmbH

Other

Collaborators

  • Claude Bernard University
  • ETH Zurich
  • King's College London
  • Leiden University Medical Center
  • MVZ Humangenetik Ulm
  • MVZ Labor Ravensburg
  • Omegametrix GmbH
  • University of Graz
  • University of Milan

Registry information

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Sep 2, 2021
Registry last updated
Feb 8, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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