Combining Fasting and Fibre Interventions to Optimise Their Gut Microbiome-mediated Health Benefits (CoFFIe)

This study builds on the knowledge that fasting provides metabolic health benefits and that prebiotic interventions can enhance the gut microbiome's metabolic output to likewise improve host health. Whether long-term fasting and dietary fibre interventions could be combined to achieve synergistic improvements in host metabolic health is however unknown. The goal is to provide a proof of concept in a human trial that supplementing 10±4 days fasting with dietary fibre synergistically improves metabolic outcomes via gut microbiome-mediated effects. To assess this, we aim to analyse gut microbiome changes, functional outputs, and key metabolic markers such as butyrate production, glycaemic control and ketosis.

The randomised controlled trial includes 75 participants and has two arms: one involving fasting with fibre supplementation (n = 50) and one involving fasting without fibre supplementation (n = 25). All participants will undergo a fasting period of 10±4 days according to the Buchinger Wilhelmi protocol, followed by a stepwise reintroduction of food of up to 4 days. As dietary fibre we will use maize-derived resistant starch type IV, selected based on its ability to stimulate beneficial gut microbes like Oscillibacter and corn starch as placebo. Two main visits will be conducted: before and at the end of the fasting period. During these visits, blood and stool samples will be collected, and questionnaires will be completed. Additionally, daily measurements of anthropometric parameters and well-being will be recorded. Stool samples will also be collected one month afterwards as a follow-up. Participants' metabolic health will be evaluated through various clinical parameters (e.g., body measurements, blood pressure, glycaemic control, ketones, well-being). Additionally, multi-omics data, including metagenomics and metabolomics, will provide insight into the composition of the microbiome, as well as its outputs and functions. Furthermore, the effects of fasting on extracellular vesicles in blood will be explored.

Study Overview

• Status: Not yet recruiting
• Conditions: Fasting; Gut Microbiome; Metabolism Changes; Overweight , Obesity; Dietary Fibre
• Intervention / Treatment: Dietary supplement: Fibre Arm; Dietary supplement: Control Arm

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elena Katharina Stroppel; Phone Number: 00497551807675; Email: katharina.stroppel@buchinger-wilhelmi.com

Study Locations

• Germany
  • Baden-Wurttemberg
    • Überlingen, Baden-Wurttemberg, Germany, 88662
      • Buchinger Wilhelmi Development & Holding
      • Contact: Elena Katharina Stroppel; Phone Number: 00497551807675; Email: katharina.stroppel@buchinger-wilhelmi.com
      • Contact: Email: forschung@buchinger-wilhelmi.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Men and women
• Age: 18-65 years old
• Fasting for 10±4 days at the Buchinger Wilhelmi clinic in Überlingen
• BMI ≥ 25 kg/m²
• Signed informed consent

Exclusion Criteria:

• intake of antibiotics up to 2 months prior the study
• regular intake of pre-, post- and probiotics up to 2 months prior the study
• diagnosed Crohn's disease, Ulcerative colitis, IBD, coeliac disease
• medicated high blood pressure
• diagnosed diabetes mellitus type I
• medicated diabetes mellitus type II
• diagnosed kidney stone
• active malignant disease
• known substance addiction
• pregnancy or breastfeeding
• diagnosed with cachexia, anorexia nervosa, advanced kidney, liver or cerebrovascular insufficiency
• inability to sign the informed consent
• participation in another study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fibre Arm; Participants (n=50) undergo a 10±4-day fasting period according to the Buchinger Wilhelmi fasting programme and receive maize-derived resistant starch type IV at a total dose of 20 g per day. The powder is blended into a carbohydrate-free electrolyte powder, divided into two equal daily doses, diluted in approximately 0.2 litres of water, and taken orally in the morning and at dinnertime throughout the fasting period. The fasting period is followed by a structured food reintroduction period according to the standard procedure of the Buchinger Wilhelmi Clinic. All other aspects of the intervention, including the fasting and nutritional protocol, clinical supervision, and study assessments, are identical to the control arm.	Dietary supplement: Fibre Arm; 10±4 days of fasting according to the Buchinger Wilhelmi fasting protocol, followed by a structured food reintroduction period, combined with 20 g/day of maize-derived resistant starch type IV.
Placebo Comparator: Control Arm; Participants (n=25) undergo a 10±4-day fasting period according to the Buchinger Wilhelmi fasting programme and receive corn starch placebo at a total dose of 1.2 g per day. The powder is blended into a carbohydrate-free electrolyte powder, divided into two equal daily doses, diluted in approximately 0.2 litres of water, and taken orally in the morning and at dinnertime throughout the fasting period. The fasting period is followed by a structured food reintroduction period according to the standard procedure of the Buchinger Wilhelmi Clinic. All other aspects of the intervention, including the fasting and nutritional protocol, clinical supervision, and study assessments, are identical to the intervention arm.	Dietary supplement: Control Arm; 10±4 days of fasting according to the Buchinger Wilhelmi fasting protocol, followed by a structured food reintroduction period, combined with 1.2 g/day of corn starch placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abundance of butyrate-producing gut bacteria	Change in the relative abundance of butyrate-producing gut bacteria assessed by metagenomic profiling of faecal samples.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in fasting venous plasma glucose	Fasting venous plasma glucose concentration measured by clinical laboratory analysis (mmol/L).	Baseline (T0) and end of the 10±4-day fasting period (T1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body weight	Body weight (kg) measured as part of the clinical health assessment.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in body mass index	Body mass index calculated from measured body weight and height (kg/m²).	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in waist circumference	Waist circumference (cm) measured as part of the clinical health assessment.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in HbA1c	HbA1c (mmol/mol) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in HOMA index	HOMA index calculated from fasting plasma glucose and fasting insulin concentrations.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in fasting venous insulin	Fasting venous insulin concentration (pmol/L) measured by clinical laboratory analysis.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in glycaemic control assessed by continuous glucose monitoring	Glycaemic control assessed by blinded continuous glucose monitoring using the FreeStyle Libre 3 system, with glucose values recorded at 1-minute intervals (mmol/L).	From Day 1 through Day 14

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the abundance of butyrate-producing gut bacteria	Exploratory assessment of the change in the abundance of butyrate-producing gut bacteria, derived from metagenomic profiling. Additional unscheduled samples may be collected during fasting if spontaneous bowel movements occur.	Baseline (T0), end of the 10±4-day fasting period (T1), and 1 month after fasting (T2)
Change in body weight	Exploratory assessment of change in body weight (kg)	Baseline (T0), daily during the 10±4-day fasting period and food reintroduction period, and 1 month after fasting (T2)
Change in body mass index	Exploratory assessment of change in body mass index (kg/m²).	Baseline (T0), daily during the 10±4-day fasting period and food reintroduction period, and 1 month after fasting (T2)
Change in glycaemic control assessed by continuous glucose monitoring	Exploratory assessment of change in glycaemic control during the post-fasting follow-up period, assessed by open-label continuous glucose monitoring.	From day 15 through day 28
Change in gut microbiome composition and functional output	Change in gut microbiome composition and functional output from baseline and the end of the fasting period to the one-month follow-up, assessed by metagenomics, metatranscriptomics, metabolomics, and short-chain fatty acid analysis. Additional unscheduled samples may be collected during fasting if spontaneous bowel movements occur	Baseline, end of the 10±4-day fasting period, and 1 month after fasting
Height	Measurement of body height (cm)	at baseline
Changes in resting blood pressure	Resting systolic blood pressure (mmHg) and resting diastolic blood pressure (mmHg) measured as part of the clinical health assessment and as self-measurement at follow-up.	Baseline (T0), daily during the 10±4-day fasting period and food reintroduction period, and 1 month after fasting (T2)
Change in heart rate	Heart rate (beats/min) measured as part of the clinical health assessment and as self-measurement at follow-up.	Baseline (T0), daily during the 10±4-day fasting period and food reintroduction period, and 1 month after fasting (T2)
Change in leucocyte count	Change in leucocyte count (10⁹/L) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in erythrocyte count	Change in erythrocyte count (10¹²/L) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in haemoglobin concentration	Change in haemoglobin concentration (g/L) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in haematocrit	Change in haematocrit levels (L/L) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in mean corpuscular volume (MCV)	Change in mean corpuscular volume (fL) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in mean corpuscular haemoglobin (MCH)	Change in mean corpuscular haemoglobin (pg) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in mean corpuscular haemoglobin concentration (MCHC)	Change in mean corpuscular haemoglobin concentration (g/L) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in thrombocyte count	Change in thrombocyte count (10⁹/L) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in lymphocyte count	Change in lymphocyte count (10⁹/L) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in international normalized ratio (INR)	Change in international normalized ratio (dimensionless) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in Quick value	Change in Quick value (%) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in partial thromboplastin time (PTT)	Change in partial thromboplastin time (seconds) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Changes in liver parameters	Liver-related parameters measured by clinical laboratory analysis of venous blood: aspartate aminotransferase (U/L), alanine aminotransferase (U/L), gamma-glutamyl transferase (U/L), and alkaline phosphatase (U/L).	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in uric acid	Change in uric acid levels (µmol/L) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in urea	Change in urea levels (mmol/L) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in creatinine	Change in creatinine levels (µmol/L) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in estimated glomerular filtration rate (eGFR)	Change in estimated glomerular filtration rate (mL/min/1.73 m²) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Changes in lipid parameters	Lipid parameters measured by clinical laboratory analysis of venous blood: total cholesterol (mmol/L), triglycerides (mmol/L), high-density lipoprotein cholesterol (mmol/L), low-density lipoprotein cholesterol (mmol/L), and non-high-density lipoprotein cholesterol (mmol/L).	Baseline (T0) and end of the 10±4-day fasting period (T1)
Changes in serum electrolyte concentrations	Electrolyte concentrations measured by clinical laboratory analysis of venous blood: sodium (mmol/L), potassium (mmol/L), calcium (mmol/L), and magnesium (mmol/L).	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in high-sensitivity C-reactive protein	High-sensitivity C-reactive protein concentration (mg/L) measured by clinical laboratory analysis of venous blood.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in extracellular vesicle size	Change in extracellular vesicle size (nm) derived from the analysis of venous blood samples.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in extracellular vesicle concentration	Change in extracellular vesicle concentration (particles/mL) derived from the analysis of venous blood samples.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Change in extracellular vesicle cargo profile	Change in extracellular vesicle cargo profile derived from the analysis of venous blood samples.	Baseline (T0) and end of the 10±4-day fasting period (T1)
Changes in urinary acetoacetic acid	Acetoacetic acid measured in urine as a biomarker of ketosis.	Baseline (T0) and daily during the 10±4-day fasting period and food reintroduction period
Change in WHO-5 well-being index	Change in WHO-5 (score: 0-100)	Baseline (T0), end of the 10±4-day fasting period (T1), and 1 month after fasting (T2)
Changes in self-reported gut health and symptoms	Questionnaire-based assessment of gastrointestinal and systemic symptoms using a 0-to-10 numerical rating scale (where 0 = none/not full and 10 = very strong/very full). Symptoms assessed include hunger, bloating/fullness, flatulence, abdominal discomfort/pain, nausea, heartburn, acid regurgitation, cravings, fatigue, headache, and sleep disturbances.	Baseline (T0), daily during the 10±4-day fasting period and food reintroduction period, end of the 10±4-day fasting period (T1), and 1 month after fasting (T2)
Change in self-reported physical activity	Change in physical activity level (hours/day) assessed by online questionnaires.	Baseline (T0), daily during the 10±4-day fasting period and food reintroduction period (Day 1 through end of reintroduction), and 1 month after fasting (T2)
Change in self-reported physical activity	Change in physical activity level (VAS 0-10) assessed by online questionnaires.	Baseline (T0), daily during the 10±4-day fasting period and food reintroduction period (Day 1 through end of reintroduction), and 1 month after fasting (T2)
Change in self-reported well-being	Change in self-reported physical and emotional well-being (VAS 0-10) as well as energy level (VAS 0-10) assessed by online questionnaires.	Baseline (T0), daily during the 10±4-day fasting period and food reintroduction period (Day 1 through end of reintroduction), and 1 month after fasting (T2)
Occurrence of adverse effects	Number and characteristics of possible adverse effects assessed from participant reports and documentation by the study physician, including seriousness and possible relationship to the study intervention.	Through study completion, an average of 7 weeks
Smoking behavior	status: never, former, current	baseline
Confounding medical events and medication	Number of participants reporting concomitant medication use, supplement intake, or medical interventions (including antibiotics, prebiotics, probiotics, postbiotics, dietary supplements, hormonal therapies, surgeries, gastrointestinal endoscopies, or hospitalizations).	Baseline (T0) and 1 month after fasting (T2)
Dietary patterns	Number of participants practicing specific dietary patterns (including omnivorous, flexitarian, pescetarian, vegetarian, vegan, or other specific diets like ketogenic).	Baseline (T0) and 1 month after fasting (T2)
Change in intake of specific food categories	Questionnaire-based assessment of dietary fiber and fermented food intake (measured in portions per day or week) across specific food categories, including fruit, vegetables, bread and grain products, nuts and seeds, legumes, and fermented foods.	Baseline (T0) and 1 month after fasting (T2)
Change in alcohol consumption	Questionnaire-based assessment of average weekly alcohol consumption (measured in standard glasses per week) across specific beverage types, including wine, beer, and spirits.	Baseline (T0) and 1 month after fasting (T2)
Change in stool consistency	Change in usual stool consistency measured by the Bristol Stool Chart (Type 1 to Type 7; coded as an ordinal category).	Baseline (T0) and 1 month after fasting (T2)
Change in bowel movement frequency	Change in typical bowel movement frequency categorized into four ordinal levels (from 1-2 times per week up to more than 3 times per day)	Baseline (T0) and 1 month after fasting (T2)
Change in general gut health rating	Change in subjective general gut health rated on a 0-to-10 numerical rating scale (where 0 = very poor and 10 = excellent).	Baseline (T0) and 1 month after fasting (T2)
Initial laxative methods	Number of participants utilizing specific laxative methods at the beginning of the fasting period (including Glauber's salt, Laxoberal, enemas, other laxatives, or no laxative use).	End of the 10±4-day fasting period (T1)
Palatability of the dietary fiber supplement	Subjective taste rating of the dietary fiber supplement measured on a 7-point Likert scale (from "not at all" to "very good").	End of the 10±4-day fasting period (T1)
Perceived change in digestion during fiber supplementation	Participant-reported change in digestion during the supplementation period, measured on a 7-point Likert scale (from "very negative" to "very positive").	End of the 10±4-day fasting period (T1)
Tolerability of the dietary fiber supplement	Subjective tolerability rating of the dietary fiber supplement measured on a 7-point Likert scale (from "very poorly" to "very well").	End of the 10±4-day fasting period (T1)
Intervention compliance	Compliance with the dietary fiber supplementation protocol, calculated as the percentage of prescribed doses successfully consumed (both morning and evening doses) during the fasting and food reintroduction periods, as verified by participant daily logs.	Daily during the 10±4-day fasting period and food reintroduction period (Day 1 through end of reintroduction)
Utilization of optional supplements during fasting	Tracking the consumption of optional dietary additions permitted within the fasting protocol. This includes the number of participants choosing to consume midday juice, honey, or other additions (such as yogurt, Kousmine cream, oatmeal, or carrot juice).	Daily during the 10±4-day fasting period (Day 1 through end of fasting (T1))
Daily bowel movement occurrence and induction method	Number of participants reporting a bowel movement each day, categorized by the method of clearance (none, spontaneous, induced by enema, induced by colon hydrotherapy, or induced by laxatives).	Daily during the 10±4-day fasting period and food reintroduction period (Day 1 through end of reintroduction)
Daily spontaneous stool consistency	Daily assessment of stool consistency for participants with spontaneous bowel movements, scored using the Bristol Stool Chart (Type 1 to Type 7; analyzed as daily ordinal categories or mean scores).	Daily during the 10±4-day fasting period and food reintroduction period (Day 1 through end of reintroduction)
Daily fluid intake	Daily self-reported volume of water or herbal tea consumed by participants, measured in liters (L).	Daily during the 10±4-day fasting period and food reintroduction period

Collaborators and Investigators

• Sponsor: Buchinger Wilhelmi Development & Holding GmbH
• Collaborators: Buchinger Wilhelmi Clinic, 88662 Überlingen, Germany; King's College London, Faculty of Life Sciences & Medicine, Department of Nutritional Sciences, London, United Kingdom; Leiden University Medical Center, Department Leiden University Center for Infectious Diseases, 2333ZA, Leiden, Netherlands; TNO, Department Microbiology & Systems Biology, 2333 BE Leiden, Netherlands; Università degli Studi di Milano, Department of Pharmacological and Biomolecular Sciences Rodolfo Paoletti, Milan, Italy; Department of Cardio-Thoracic-Vascular Diseases, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
• Investigators: Principal Investigator: Andrea Siegler, Dr. med., Buchinger Wilhelmi Development & Holding

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: June 24, 2026
• First Submitted That Met QC Criteria: July 2, 2026
• First Posted (Actual): July 9, 2026

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: gut microbiome; continuous glucose monitoring; fasting; metabolomics; ketosis; metabolic health; extracellular vesicles; long-term fasting; fibre supplementation; resistant starch IV
• Additional Relevant MeSH Terms: Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Acid-Base Imbalance; Acidosis; Pathological Conditions, Signs and Symptoms; Behavior; Nutritional and Metabolic Diseases; Signs and Symptoms; Feeding Behavior; Overweight; Obesity; Ketosis; Fasting
• Other Study ID Numbers: F-2026-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No