The goal of this double-blinded randomized clinical cross-over trial is to investigate the metabolic and appetite regulating effects of oral tributyrin (a butyrate pro-drug) administration vs placebo. The main questions it aims to answer are: * Does tributyrin have glucose lowering properties in humans? * Does tributyrin reduce appetite in humans? A sample size calculation estimated a minimum of 10 participants. We expect to include 12 participants in this study. Tributyrin or placebo is ingested once or twice daily for 2x2 weeks, separated by a washout period of minimum 2 weeks. On trial day following each 2-week period we assess: * Postprandial blood sugar levels * Hunger sensations (questionnaire) * Enteroendocrine hormone secretion (GLP-1, GIP, PYY, LEAP2, ghrelin) * Cardiac function (echocardiography) - An exploratory study evaluating the hemodynamic effects assessed by echocardiography is anticipated to be published separately. * Caloric intake (ad libitum meal test) * Gastric emptying rate (acetaminophen test) * Resting metabolic rate (indirect calorimetry). While at home, subjects will wear a sleep monitoring device for three consecutive nights and deliver fecal samples for analysis of short-chain fatty acid content and microbiota composition.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
12
Oral ingestion of tributyrin (liquid) once daily (20 g x 1) for 7 days, then twice daily (20 g x 2) for 7 days.
Oral ingestion of water (liquid) with added bitter substance once daily (20 ml x 1) for 7 days, then twice daily (20 ml x 2) for 7 days
SDCA / Medical Research Laboratory
Aarhus N, Denmark
RECRUITINGPostprandial glucose
iAUC of plasma glucose after ingestion of mixed meal
Time frame: During trial day, time 120-300 minutes
Butyrate
Plasma concentrations of butyrate
Time frame: During trial day, time 0-300 minutes
Subjective appetite - appetite questionaire
We will assess subjective appetite sensations with a recommended primary scale for self-reported appetite in healthy adults. The scale includes five questions addressing hunger, fullness, satiety, desire to eat and prospective consumption. The participants answer on a computer or tablet by sliding a button on a horizontal line (Visual Analog Scale) with left being eg. "Not hungry at all" to right "As hungry as I have ever felt".
Time frame: 0, 60, 120, 180, 240, 300 minutes
Caloric intake
Caloric intake (kcal) during ad libitum meal test
Time frame: Time 300 minutes
Gastric emptying assessed by acetaminophen
Plasma concentration of acetaminophen following oral acetaminophen intake
Time frame: From ingestion of mixed meal test with acetaminophen, time 120-240 minutes
GLP-1
Plasma concentrations of GLP-1
Time frame: During trial day, time 0-300 minutes
GIP
Plasma concentrations of GIP
Time frame: During trial day, time 0-300 minutes
LEAP2
Plasma concentrations of LEAP2
Time frame: During trial day, time 0-300 minutes
PYY
Plasma concentrations of PYY
Time frame: During trial day, time 0-300 minutes
Ghrelin
Plasma concentrations of ghrelin
Time frame: During trial day, time 0-300 minutes
Insulin
Plasma concentrations of insulin
Time frame: During trial day, time 0-300 minutes
C-peptide
Plasma concentrations of c-peptide
Time frame: During trial day, time 0-300 minutes
Glucagon
Plasma concentrations of glucagon
Time frame: During trial day, time 0-300 minutes
Cardiac function
Echocardiographic assessment of cardiac output, left ventricular ejection fraction, global longitudinal strain, tricuspid annular plane systolic excursion (TAPSE), systemic vascular resistance
Time frame: Time 0 and 90 minutes
β-hydroxybutyrate
Plasma concentrations of β-hydroxybutyrate
Time frame: During trial day, time 0-300 minutes
Lactate
Plasma concentrations of lactate
Time frame: During trial day, time 0-300 minutes
C-reactive protein (CRP)
Plasma concentrations of CRP
Time frame: On trial day, time 0 minutes
Tumor Necrosis Factor ⍺ (TNF-⍺)
Plasma concentrations of TNF-⍺
Time frame: On trial day, time 0 minutes
Interleukin 6 (IL-6)
Plasma concentrations of IL-6
Time frame: On trial day, time 0 minutes
Interleukin 10 (IL-10)
Plasma concentrations of IL-10
Time frame: On trial day, time 0 minutes
Lipopolysaccharide Binding Protein (LPB)
Plasma concentrations of LPB
Time frame: On trial day, time 0 minutes
Cortisol
Plasma concentration of cortisol
Time frame: On trial day, time 0 minutes
Triglyceride
Plasma concentrations of triglyceride
Time frame: During trial day, time 0-300 minutes
FFA
Plasma concentrations of free fatty acids
Time frame: During trial day, time 0-300 minutes
Energy expenditure
Indirect calorimetry
Time frame: After 60 and 150 minutes approximately
Sleep
Assessment of sleep duration and stages
Time frame: Three nights at the end of the 2 week period at home
Fecal butyrate
Fecal concentrations of butyrate
Time frame: Day 0, 7, 14 during the 2 week period
Microbiome composition
Analysis of microbiome composition and metagenomics performed on fecal samples
Time frame: Day 0, 7, 14 during the 2 week period
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.