Metabolic Effects of Four-week Lactate-ketone Ester Supplementation
- Conditions
- Obesity
- Interventions
- Dietary Supplement: PlaceboDietary Supplement: LaKe Ester
- Registration Number
- NCT05917873
- Lead Sponsor
- University of Aarhus
- Brief Summary
Recent research reveals intriguing results concerning the role of exogenous lactate and the ketone body 3-hydroxybutyrate (3-OHB) as therapeutic tools to combat obesity and related conditions. Thus, oral administration of lactate and 3-OHB have separately been shown to suppress appetite sensations and slow gastric emptying while administered orally. Both seem to inhibit lipolysis while oral 3-OHB administration have shown direct insulin sensitizing effects. Furthermore, both substrates can be used as fuel for the heart.
The goal of this placebo-controlled randomized crossover design is to test exogenous lactate and the ketone body 3-hydroxybutyrate (3-OHB) in healthy, non-diabetic, obese adults.
The main questions it aims to answer are if chronic administration of LaKe ester affect or improve the following endpoints:
* Insulin sensitivity
* Appetite sensations
* Gastric emptying
* Lipolysis
* Cardiac output
* Left Ventricular Ejection Fraction
* Global Longitudinal Strain and other echocardiographic measures listed below
Participants will ingest a combined lactate and ketone body ester (LaKe ester) or placebo twice a day for 28 days before experimental days.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 10
- Age between 30-60 years
- BMI range 30-40
- Glycated haemoglobin (HbA1c) < 48 mmol/mol
- Otherwise 'healthy'
- Written and oral consent
- Medication that affect energy or glucose metabolism, eg metformin, insulin or Glucagon-like peptide-1 receptor (GLP-1) agonists
- Specific diets (eg practicing ketogenic diets)
- Cardiac arrhythmias (eg atrial fibrillation)
- Ongoing acute/chronic serious diseases (eg, anemia, chronic kidney or liver disease)
- Inability to understand Danish or English
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo arm Placebo Placebo treatment LaKe arm LaKe Ester Ingestion of a combined lactate and ketone body ester, 25 ml twice daily for 28 days.
- Primary Outcome Measures
Name Time Method Insulin sensitivity expressed as an M-value Throughout the cross-over design, approximately 12 weeks On all study days, a hyperinsulinemic-euglycemic clamp is used to determine insulin sensitivity: continuous infusion of insulin (1 milliunit · kg lean body mass-1 · min-1) for 2 hours. The blood glucose is clamped at 5 mmol/l.
- Secondary Outcome Measures
Name Time Method Mitral inflow velocities (E and A) Throughout the cross-over design, approximately 12 weeks Echocardiographic changes
Changes in blood concentrations of 3-OHB Throughout the cross-over design, approximately 12 weeks Blood sampling
Mitral plane velocities in the lateral mitral annulus (e' and s') Throughout the cross-over design, approximately 12 weeks Echocardiographic changes
Changes in blood concentrations of lactate Throughout the cross-over design, approximately 12 weeks Blood sampling
Differences in lipolysis rate Throughout the cross-over design, approximately 12 weeks Measured as differences in palmitate flux
Tricuspid annular plane systolic excursion (TAPSE) Throughout the cross-over design, approximately 12 weeks Echocardiographic changes
Differences in body weight and composition Throughout the cross-over design, approximately 12 weeks Dual-energy X-ray absorptiometry (DEXA) scan to assess total fat mass (kg), lean body mass (kg), and bone mass (kg)
Cardiac Output (CO) Throughout the cross-over design, approximately 12 weeks Echocardiographic changes in left ventricular outflow tract (LVOT), velocity time integral (VTI) and heart rate (HR)
Global Longitudinal Strain (GLS) Throughout the cross-over design, approximately 12 weeks Echocardiographic changes
Changes in blood concentrations of free fatty acids Throughout the cross-over design, approximately 12 weeks Blood sampling
Changes in blood concentrations of gastric inhibitory polypeptide (GIP) Throughout the cross-over design, approximately 12 weeks Blood sampling
Changes in blood concentrations of glucagon Throughout the cross-over design, approximately 12 weeks Blood sampling
Changes in blood concentrations of triglycerides Throughout the cross-over design, approximately 12 weeks Blood sampling
Changes in blood concentrations of cholesterol Throughout the cross-over design, approximately 12 weeks Blood sampling
Changes in blood concentrations of brain-derived neurotrophic factor (BDNF) Throughout the cross-over design, approximately 12 weeks Blood sampling
Differences in gastric emptying rate Throughout the cross-over design, approximately 12 weeks Evaluated by using the acetaminophen test
Global work index (GWI) Throughout the cross-over design, approximately 12 weeks Echocardiographic changes
Changes in blood concentrations of glucose Throughout the cross-over design, approximately 12 weeks Blood sampling
Changes in blood concentrations of insulin Throughout the cross-over design, approximately 12 weeks Blood sampling
Changes in blood concentrations of C-peptide Throughout the cross-over design, approximately 12 weeks Blood sampling
Fibrosis-4 (FIB-4) Throughout the cross-over design, approximately 12 weeks Blood sampling of alanine aminotransferase (ALAT), aspartate transaminase (ASAT), and thrombocytes
Left Ventricular Ejection Fraction (LVEF) Throughout the cross-over design, approximately 12 weeks Echocardiographic changes
Changes in plasma concentrations of growth/differentiation factor 15 (GDF-15) Throughout the cross-over design, approximately 12 weeks Blood sampling
Mood, assessed by Major Depression Inventory score (MDI) Throughout the cross-over design, approximately 12 weeks Change in MDI score measured by Major Depression Inventory. The theoretical sum score ranges from 0 (no depression) to 50 (maximum depression).
Changes in blood concentrations of N-lactoyl-phenylalanine (Lac-Phe) Throughout the cross-over design, approximately 12 weeks Blood sampling
Changes in blood concentrations of erythrocyte volume fraction (EVF) Throughout the cross-over design, approximately 12 weeks Blood sampling
Changes in blood concentrations of Erythropoietin (EPO) Throughout the cross-over design, approximately 12 weeks Blood sampling
Changes in blood concentrations of ghrelin Throughout the cross-over design, approximately 12 weeks Blood sampling
Changes in blood concentrations of liver-expressed antimicrobial peptide 2 (LEAP-2) Throughout the cross-over design, approximately 12 weeks Blood sampling
Changes in blood concentrations of inflammation markers Throughout the cross-over design, approximately 12 weeks Blood sampling of C reactive protein (CRP) and leucocytes
Anxiety Symptom Scale questionnaire (ASS) Throughout the cross-over design, approximately 12 weeks Change in the Anxiety Symptom Scale questionnaire to screen for anxiety disorders. The theoretical sum score ranges from 0 (no anxiety) to 60 (maximum anxiety).
Supplement tolerability Throughout the cross-over design, approximately 12 weeks Assessed using a symptom questionnaire covering every organ system, including GI symptoms measured through the validated "Beverage Tolerability Questionnaire". Participants will rate the frequency of each item on a scale from 0 (no symptoms) to 5 (severe symptoms).
Control of Eating Questionnaire (CoEQ) Throughout the cross-over design, approximately 12 weeks The CoEQ has been used in clinical trials as a multi-dimensional measure of appetite, craving and mood regulation. Based on the previous 7 days, subjects will be asked to answer 21 questions (20 rated on a 100 mm visual analogue scale and one open-ended).
Trial Locations
- Locations (1)
Steno Diabetes Center Aarhus
🇩🇰Aarhus, Denmark