Metabolic Effects of Four-week Lactate-ketone Ester Supplementation

Not Applicable

Active, not recruiting

• Conditions: Obesity

• 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

Study Timeline

• Study First Submitted: 2023-06-05
• Study First Submitted QC: 2023-06-14
• Study First Posted: 2023-06-26
• Study Start: 2023-09-07
• Status Verified: 2024-10
• Last Update Submitted: 2025-04-01
• Last Update Posted: 2025-04-04
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

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 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
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).
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
Changes in plasma concentrations of growth/differentiation factor 15 (GDF-15)	Throughout the cross-over design, approximately 12 weeks	Blood sampling

Trial Locations

Locations (1)

Steno Diabetes Center Aarhus; 🇩🇰 Aarhus, Denmark