Fasting or a Fasting Mimicking diet (FMD) can lower blood concentration of glucose and IGF1. Since cancer cells rely mostly on a glucose-based metabolism, FMD renders cancer cells more vulnerable to chemotherapy, thereby enhancing therapeutic efficacy. This process is known as differential stress sensitization (DSS). Another response to nutritional stress by fasting is known as differential stress resistance (DSR). DSR is a state in which healthy cells rather focus resources on protection and internal repair, which can result in reduced chemotherapeutic toxicity. Recent preclinical studies found that fasting or FMD not only aids healthy cell protection, but also has the potential to benefit effector T-cells and could thereby improve antitumor immunity. However in most oncotherapeutic clinical trials investigating the addition of a fasting regimen, other factors such as chemotherapy, surgery and additional medication affect the immune system as well. That is why this explorative study, conducted in healthy subjects, might be more suitable to investigate the immunological alterations upon FMD more specifically. This exploratory study aims to identify immunological alterations by using extensive immunoprofiling before and after three days of FMD in healthy subjects, as well as investigate possible side effects of FMD.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
16
Low-caloric, low-protein, plant-based diet regiment for 3 days
Leiden University Medical Center
Leiden, South Holland, Netherlands
Change in gene expression signature in peripheral blood mononuclear cells (PBMCs) after overnight fast and after completion of 2 cycles of fasting mimicking diet compared to baseline.
PBMCs are retrieved from whole blood samples. Gene expression signature is retrieved from PBMCs using RNA-Nanostring technique with the Pancancer IO 360 panel. The Nanostring will report RNA counts for a panel of 770 genes, including 40 housekeeping genes. The data will be normalized on the 40 housekeeping genes for internal control using Nanostring nSolver software. The fold change from baseline to overnight fast and after completion of second fasting mimicking diet will provide insight in affected pathways as well as metabolic and immune signatures.
Time frame: 4 weeks
Change in immune cell properties from PBMCs after overnight fast and after 2 cycles of fasting mimicking diet compared to baseline.
PBMCs retrieved from whole blood samples will be analysed with a 40-plex Aurora flowcytometry panel with markers for T cells and myeloid cells. The flow cytometry will generate frequencies of the different immune cell markers,. A comparison of the frequency data between blood samples will determine change in immune cell properties. This analysis will be used to confirm and complement gene expression signature findings on a protein level.
Time frame: 6 months
Change in plasma concentration of IGF1, glucose and ketone bodies (Beta-hydroxybutyric acid) after overnight fast and after completion of 2 cycles of fasting mimicking diet compared to baseline.
Measured in blood plasma taken at 3 time points.
Time frame: 4 weeks
Percentage of participants reporting adverse events as assessed by CTCAE v5.0 during fasting mimicking diet
Descriptive analysis of adverse events by type and grade according to NCI CTCAE v5.0 experienced by participants during fasting mimicking diet assessed after second cycle on day 22.
Time frame: 8 weeks
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