MetaLaKe: Metabolic Effects of Four-week Lactate-ketone Ester Supplementation
Study Details
Study Description
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.
The goal of this placebo-controlled randomized crossover design is to test exogenous lactate and the ketone body 3-hydroxybutyrate (3-OHB) in non-diabetic, obese adults.
The main questions it aims to answer are if chronic administration of LaKe ester affect or improve the following endpoints related to obesity:
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Insulin sensitivity
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Appetite sensations
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Gastric emptying
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Lipolysis
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Cardiac output
Participants will ingest a combined lactate and ketone body ester (LaKe ester) or placebo twice a day for 28 days before experimental days.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LaKe arm Ingestion of a combined lactate and ketone body ester, 25 ml twice daily for 28 days. |
Dietary Supplement: LaKe Ester
Lactate and ketone body ester (one equivalent of S-lactate and one equivalent of 1,3-butanediol / D-β-hydroxybutyrate)
|
| Placebo Comparator: Placebo arm Placebo treatment |
Dietary Supplement: Placebo
Taste and appearance matched noncaloric placebo
|
Outcome Measures
Primary Outcome Measures
- Insulin sensitivity expressed as an M-value [3 months from baseline throughout the cross-over design]
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
- Differences in lipolysis rate [3 months from baseline throughout the cross-over design]
Measured as differences in palmitate flux
- Differences in body weight and composition [3 months from baseline throughout the cross-over design]
Dual-energy X-ray absorptiometry (DEXA) scan to assess total fat mass (kg), lean body mass (kg), and bone mass (kg)
- Differences in gastric emptying rate [3 months from baseline throughout the cross-over design]
Evaluated by using the acetaminophen test
- Cardiac Output (CO) [3 months from baseline throughout the cross-over design]
Echocardiographic changes in left ventricular outflow tract (LVOT), velocity time integral (VTI) and heart rate (HR)
- Left Ventricular Ejection Fraction (LVEF) [3 months from baseline throughout the cross-over design]
Echocardiographic changes
- Tricuspid annular plane systolic excursion (TAPSE) [3 months from baseline throughout the cross-over design]
Echocardiographic changes
- Global Longitudinal Strain (GLS) [3 months from baseline throughout the cross-over design]
Echocardiographic changes
- Mitral inflow velocities (E and A) [3 months from baseline throughout the cross-over design]
Echocardiographic changes
- Mitral plane velocities in the lateral mitral annulus (e' and s') [3 months from baseline throughout the cross-over design]
Echocardiographic changes
- Global work index (GWI) [3 months from baseline throughout the cross-over design]
Echocardiographic changes
- Changes in blood concentrations of 3-OHB [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in blood concentrations of lactate [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in blood concentrations of free fatty acids [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in blood concentrations of glucose [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in blood concentrations of insulin [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in plasma concentrations of growth/differentiation factor 15 (GDF-15) [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in blood concentrations of gastric inhibitory polypeptide (GIP) [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in blood concentrations of ghrelin [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in blood concentrations of glucagon [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in blood concentrations of liver-expressed antimicrobial peptide 2 (LEAP-2) [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in blood concentrations of C-peptide [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in blood concentrations of triglycerides [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in blood concentrations of cholesterol [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in blood concentrations of brain-derived neurotrophic factor (BDNF) [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in blood concentrations of N-lactoyl-phenylalanine (Lac-Phe) [3 months from baseline throughout the cross-over design]
Blood sampling
- Fibrosis-4 (FIB-4) [3 months from baseline throughout the cross-over design]
Blood sampling of alanine aminotransferase (ALAT), aspartate transaminase (ASAT), and thrombocytes
- Changes in blood concentrations of erythrocyte volume fraction (EVF) [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in blood concentrations of Erythropoietin (EPO) [3 months from baseline throughout the cross-over design]
Blood sampling
- Changes in blood concentrations of inflammation markers [3 months from baseline throughout the cross-over design]
Blood sampling of C reactive protein (CRP) and leucocytes
- Mood, assessed by Major Depression Inventory score (MDI) [3 months from baseline throughout the cross-over design]
Change in MDI score measured by Major Depression Inventory. The theoretical sum score ranges from 0 (no depression) to 50 (maximum depression).
- Anxiety Symptom Scale questionnaire (ASS) [3 months from baseline throughout the cross-over design]
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 [3 months from baseline throughout the cross-over design]
Assessed using a symptom questionnaire covering every organ system, including GI symptoms. Participants will rate the frequency of each item using the 100 mm visual analogue scale (VAS).
- Control of Eating Questionnaire (CoEQ) [3 months from baseline throughout the cross-over design]
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 VAS and one open-ended).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age between 30-60 years
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BMI range 30-40
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Glycated haemoglobin (HbA1c) < 48 mmol/mol
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Otherwise 'healthy'
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Written and oral consent
Exclusion Criteria:
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Medication that affect energy or glucose metabolism, eg metformin, insulin or Glucagon-like peptide-1 receptor (GLP-1) agonists
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Specific diets (eg practicing ketogenic diets)
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Cardiac arrhythmias (eg atrial fibrillation)
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Ongoing acute/chronic serious diseases (eg, anemia, chronic kidney or liver disease)
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Inability to understand Danish or English
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- University of Aarhus
- Novo Nordisk A/S
- Aarhus University Hospital
- Riisfort
Investigators
- Study Director: Niels Møller, Professor, Aarhus University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 98128