Metabolic Effects of Four-week Lactate-ketone Ester Supplementation (MetaLaKe)

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Dietary supplement: LaKe Ester; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Steno Diabetes Center Aarhus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age between 30-60 years
• BMI range 30-40
• Glycated haemoglobin (HbA1c) < 48 mmol/mol
• Otherwise 'healthy'
• Written and oral consent

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity expressed as an M-value	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.	Throughout the cross-over design, approximately 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in lipolysis rate	Measured as differences in palmitate flux	Throughout the cross-over design, approximately 12 weeks
Differences in body weight and composition	Dual-energy X-ray absorptiometry (DEXA) scan to assess total fat mass (kg), lean body mass (kg), and bone mass (kg)	Throughout the cross-over design, approximately 12 weeks
Differences in gastric emptying rate	Evaluated by using the acetaminophen test	Throughout the cross-over design, approximately 12 weeks
Cardiac Output (CO)	Echocardiographic changes in left ventricular outflow tract (LVOT), velocity time integral (VTI) and heart rate (HR)	Throughout the cross-over design, approximately 12 weeks
Left Ventricular Ejection Fraction (LVEF)	Echocardiographic changes	Throughout the cross-over design, approximately 12 weeks
Tricuspid annular plane systolic excursion (TAPSE)	Echocardiographic changes	Throughout the cross-over design, approximately 12 weeks
Global Longitudinal Strain (GLS)	Echocardiographic changes	Throughout the cross-over design, approximately 12 weeks
Mitral inflow velocities (E and A)	Echocardiographic changes	Throughout the cross-over design, approximately 12 weeks
Mitral plane velocities in the lateral mitral annulus (e' and s')	Echocardiographic changes	Throughout the cross-over design, approximately 12 weeks
Global work index (GWI)	Echocardiographic changes	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of 3-OHB	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of lactate	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of free fatty acids	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of glucose	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of insulin	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in plasma concentrations of growth/differentiation factor 15 (GDF-15)	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of gastric inhibitory polypeptide (GIP)	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of ghrelin	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of glucagon	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of liver-expressed antimicrobial peptide 2 (LEAP-2)	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of C-peptide	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of triglycerides	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of cholesterol	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of brain-derived neurotrophic factor (BDNF)	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of N-lactoyl-phenylalanine (Lac-Phe)	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Fibrosis-4 (FIB-4)	Blood sampling of alanine aminotransferase (ALAT), aspartate transaminase (ASAT), and thrombocytes	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of erythrocyte volume fraction (EVF)	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of Erythropoietin (EPO)	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Changes in blood concentrations of inflammation markers	Blood sampling of C reactive protein (CRP) and leucocytes	Throughout the cross-over design, approximately 12 weeks
Mood, assessed by Major Depression Inventory score (MDI)	Change in MDI score measured by Major Depression Inventory. The theoretical sum score ranges from 0 (no depression) to 50 (maximum depression).	Throughout the cross-over design, approximately 12 weeks
Anxiety Symptom Scale questionnaire (ASS)	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).	Throughout the cross-over design, approximately 12 weeks
Supplement tolerability	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).	Throughout the cross-over design, approximately 12 weeks
Control of Eating Questionnaire (CoEQ)	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).	Throughout the cross-over design, approximately 12 weeks

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Novo Nordisk A/S; Aarhus University Hospital; Riisfort
• Investigators: Study Director: Niels Møller, Professor, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2023
• Primary Completion (Actual): December 11, 2024
• Study Completion (Actual): December 11, 2024

Study Registration Dates

• First Submitted: June 5, 2023
• First Submitted That Met QC Criteria: June 14, 2023
• First Posted (Actual): June 26, 2023

Study Record Updates

• Last Update Posted (Estimated): August 28, 2025
• Last Update Submitted That Met QC Criteria: August 21, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Insulin sensitivity; Appetite; Lipolysis
• Additional Relevant MeSH Terms: Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Hyperinsulinism; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Insulin Resistance; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: 98128

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No