Investigation of the Relationship Between Peripheral and Central Metabolic Changes Caused by Fasting

Nils Opel12 enrolled

Overview

Fasting has become an increasingly popular intervention for improving both physical and mental health. This study aims to explore the biological mechanisms underlying the positive effects of low caloric fasting (Wilhelmi-Buchinger-fasting). Specifically, we focus on the metabolic transition from glucose to fat utilization and its effects on systemic and brain metabolism. By examining the relationship between peripheral metabolic changes and brain metabolism, this research aims to uncover how these shifts influence brain metabolism and behaviour.

Therapeutic fasting, specifically Buchinger fasting, is a widely recognized method in integrative medicine. It is frequently used to treat a variety of chronic diseases, including inflammatory and metabolic disorders. In addition to its benefits for physical health, fasting is increasingly recognized for its potential to improve mental health. Research has shown that fasting can induce significant biological effects, including the metabolic switch, which involves the transition from glucose to fat as the primary energy source. This shift typically occurs around day two of the fasting period and has important implications for peripheral metabolism. However, little is known about how these peripheral metabolic changes are linked to brain metabolism and how this connection might affect brain network function and, ultimately, psychological and cognitive processes. Recent studies have shown that fasting influences both peripheral metabolism and brain function, with potential benefits for mental health. The precise mechanisms and timing of these changes remain unclear. The current study will focus on understanding (i) how peripheral metabolic changes during fasting relate to central metabolic changes in the brain, (ii) how these changes affect brain network function over time, and (iii) the connection between these metabolic and functional brain changes with psychological and cognitive alterations during fasting. This study will use detailed metabolic profiling and neuroimaging techniques, alongside psychological assessments, to explore these complex interactions in healthy, fasting individuals, providing a foundation for further research into its potential as an intervention for mental health disorders.

Study Type

INTERVENTIONAL

Allocation

Purpose

Conditions

Healthy

Interventions

FastingOTHER

Participants undergo the standardised Wilhelmi-Buchinger fasting intervention, which consists of two days of preparation with a dietary energy supply of \<1000 kcal, three days of fasting with a dietary energy supply of 300-500 kcal with tea, broth, fruit and vegetable juices, and two days of recovery.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Normal weight at study inclusion (BMI 18.5-25) * Generally good physical condition without serious previous illnesses * For female participants, only participants taking hormonal contraception are included Exclusion Criteria: * MRI contraindication: cardiac pacemakers, hearing aids, neurostimulation, insulin pumps, other potentially ferromagnetic implants, screws, clips, prostheses, metal splinters, etc., pregnancy, claustrophobia, extensive tattoos, medication that impairs thermoregulation * Comorbidity: neurological or psychiatric conditions, cognitive impairments, chronic somatic disorders * Intake of more than 40g of pure alcohol (for men) or more than 20g of pure alcohol (for women), smoking, regular drug use * Pregnancy or nursing * Current or within the past five years eating disorder, vegan diet or fasting within the past six months * Regular medication intake

Locations (1)

Department of Psychiatry and Psychotherapy, University Hospital Jena

Jena, Thuringia, Germany

Outcomes

Primary Outcomes

MR spectroscopy

metabolites between 0-4 ppm in regions including the posterior cingulate cortex (PCC), medial cingulate cortex (MCC), and anterior insula

Time frame: Outcome measures are assessed as changes from baseline over 3 fasting days, with follow-up on day 4 during refeeding, during a one-week on-site visit per participant, within an overall study period of 2 months

Secondary Outcomes

Structural MR imaging

cortical thickness, grey matter volume

Functional MRI

resting state functional connectivity

Exploratory Proteomics of Autophagy Processes II

protein levels and protein phosphorylation by targeted and untargeted mass spectrometry-based proteomics and phosphoproteomics of isolated PBMCs (peripheral blood mononuclear cells)

Exploratory Proteomics of Autophagy Processes I

protein levels of autophagy biomarkers (e.g. LC3II \& p62) of isolated PBMCs (peripheral blood mononuclear cells) by Western Blotting

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Neuropsychology: Verbal Fluency

MWT-B, Regensburg Word Fluency Test. A composite score for verbal fluency will be derived from the Regensburg Word Fluency Test and the MWT-B. First, raw scores for each test will be converted to standardized scores (e.g., z-scores). If needed, scores will be adjusted so that higher values consistently represent better performance. The standardized scores will then be averaged to create a single composite measure of verbal fluency.

Neuropsychology: Memory

VLMT-A, block span. A composite memory score will be computed from the VLM-T and Block Span test. Raw scores from each test will be standardized (e.g., into z-scores). These z-scores will then be averaged to yield a single measure of memory performance, reflecting both verbal and visuospatial working memory components.

Neuropsychology: Processing speed

Number Symbol Test, Letter-Number-Symbol Test, TMT-A. A composite score for processing speed will be derived from the Number Symbol Test, Letter-Number Symbol Test, and TMT-A. First, raw scores from each test will be normalized (e.g., converted into z-scores), taking into account that lower completion times on the TMT-A indicate better performance. The normalized scores will then be combined-after adjusting the direction of scores if necessary-by calculating their average to yield a single, unified measure of processing speed.

Neuropsychology: Attention

TMT-B, D2-Test. A composite attention score will be created using the D2-Test and TMT-B. Raw scores from both tests will be standardized (e.g., as z-scores). For tests such as the TMT-B, if necessary, the scores will be adjusted (e.g., reverse-coded) so that higher values indicate better attention performance. The resulting standardized scores will be averaged to form a unified attention measure.

Sleep

Pittsburgh Sleep Quality Index (PSQI). The 19 self-rated questions of the PSQI are grouped into 7 components. Each component is scored from 0 to 3 points. The scores of the 7 components are then summed to yield a global score ranging from 0 to 21, with higher scores indicating poorer sleep quality.

Depression

Beck's depression inventory (BDI-II). The questionnaire consists of 21 questions. Each question is scored on a 4-point scale ranging from no impairment (0) to severe impairment (3). The maximum score is 63.

Anxiety

State-Anxiety Inventory (STAI-S). For the STAI-S assessment, specific items (1, 2, 5, 8, 10, 11, 15, 16, 19, and 20) were reverse-coded because they represent aspects of anxiety expressed in a negative direction. After recoding, responses for all STAI-S items were summed to obtain the final test score for state anxiety.

Anhedonia

Snaith-Hamilton-Pleasure-Scale (SHAPS). For scoring, each non-affirmative response ("does not apply" or "does not apply at all") is assigned 1 point, while each affirmative response is assigned 0 points. The points are summed across all items, resulting in a total score ranging from 0 to 14, with higher scores indicating a greater degree of anhedonia.

Life quality

Positive Mental Health Scale. 9 items rated on a 4-point Likert scale ranging from 0 ("do not agree") to 3 ("completely agree"). A total score is computed by summing the responses to all items, with higher scores indicating greater positive mental health.

Numeric Analog Scales

Assessing mood on 0-10 points and sleep duration on 0-13 points scale

Metabolic processes

Targeted and quantitative analysis by mass spectrometry of change in metabolites of plasma

Fatigue

Fatigue Assessment Scale (FAS), 10-item self-assessment scale. For scoring, responses to items 1-3 and 5-9 are rated on a scale from 1 to 5, while items 4 and 10 are reverse-coded (scored from 5 to 1). The scores for all items are then summed to produce the total FAS score.

Lipid profiling

Targeted and quantitative analysis by mass spectrometry of change in plasma lipids

Transcription expression patterns

Change of the gene expression profile by RNA sequencing of isolated PBMCs (peripheral blood mononuclear cells)

Proteome/phosphoproteome/ubiquitinome patterns

proteome expression patterns through blood (PBMCs and Plasma) based proteome, phosphoproteome, and ubiquitinome analysis

Exosomal protein patterns

Evaluate exosomal protein content through blood based metabolome analysis