Endogenous vs. Exogenous Ketone Bodies

Impact of Endogenous vs. Exogenous Ketone Bodies on Appetite Control and Macronutrient Oxidation

Aim of the study is to compare the origin of ketone bodies: endogenous ketone bodies due to 36 hours fasting or 24 hours of ketogenic diet vs. exogenous ketone bodies as supplements additional to normal diet.

Secondary aim of the study is to validate the new metabolic chambers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: Beta-Hydroxybutyrate as Ca-Mg-salt, active; Dietary supplement: ketogenic diet (KetoCal® 4:1 Neutral, Nutricia GmbH, Erlangen, Germany), active; Dietary supplement: fasting, active; Dietary supplement: fasting, inactive

Detailed Description

Each study week starts with a 3-day run-in period with controlled diet at home and ends with a test-meal (breakfast) in the lab and following food record over the rest of the day at home.

1. week: physical activity level (PAL) 1.3, 3 intervention days in the metabolic chamber: ad libitum energy intake, washout day, isocaloric diet, 36 hours fasting
2. week: physical activity level (PAL) 1.3, 2 intervention days in the metabolic chamber: isocaloric diet, 36 hours fasting
3. week: physical activity level (PAL) 1.6, 2 intervention days in the metabolic chamber: ad libitum energy intake, 36 hours fasting
4. week: physical activity level (PAL) 1.6, 2 intervention days in the metabolic chamber: isocaloric diet, ketogenic diet (isocaloric)
5. week: physical activity level (PAL) 1.6, 2 intervention days in the metabolic chamber: isocaloric diet, isocaloric diet + ketone body supplements (isocaloric)

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Kiel, Germany, 24105
    • Institute of Human Nutrition

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• healthy
• BMI 19-29 kg/m2
• low-medium habitual physical activity
• women using hormonal contraceptive

Exclusion Criteria:

• smoking
• chronic illnesses
• food allergies / intolerances
• vegans and vegetarians
• regular high physical activity (exercise >1 hour/d)
• current weight loss diet / weight loss of >5 kg in the last 3 months
• pregnant / lactating women
• persons incapable of giving informed legal consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: fasting, active; 36 hours fasting, PAL 1.6	Dietary supplement: Beta-Hydroxybutyrate as Ca-Mg-salt, active; 24 hour intervention with ketone body supplements additional to a normal diet (isocaloric diet in total) to induce ketosis (exogenous ketone bodies), in a metabolic chamber at physical activity level of 1.6, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.6.; Dietary supplement: ketogenic diet (KetoCal® 4:1 Neutral, Nutricia GmbH, Erlangen, Germany), active; 24 hour interventions with ketogenic isocaloric diet to induce ketosis (endogenous ketone bodies), in a metabolic chamber at physical activity level of 1.6, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.6.; Dietary supplement: fasting, active; 36 hours of fasting, in a metabolic chamber at physical activity level of 1.6, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.6.; Dietary supplement: fasting, inactive; 36 hours of fasting, in a metabolic chamber at physical activity level of 1.3, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.3. The same intervention is reproduced one week later.
Experimental: ketogenic diet, active; 24 hours of ketogenic diet (liquid meals), PAL 1.6	Dietary supplement: Beta-Hydroxybutyrate as Ca-Mg-salt, active; 24 hour intervention with ketone body supplements additional to a normal diet (isocaloric diet in total) to induce ketosis (exogenous ketone bodies), in a metabolic chamber at physical activity level of 1.6, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.6.; Dietary supplement: ketogenic diet (KetoCal® 4:1 Neutral, Nutricia GmbH, Erlangen, Germany), active; 24 hour interventions with ketogenic isocaloric diet to induce ketosis (endogenous ketone bodies), in a metabolic chamber at physical activity level of 1.6, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.6.; Dietary supplement: fasting, active; 36 hours of fasting, in a metabolic chamber at physical activity level of 1.6, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.6.; Dietary supplement: fasting, inactive; 36 hours of fasting, in a metabolic chamber at physical activity level of 1.3, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.3. The same intervention is reproduced one week later.
Experimental: exogeneous ketone bodies, active; 24 hours of ketone body supplements (Beta-Hydroxybutyrate as Ca-Mg-salt) additional to a normal diet (liquid meals), PAL 1.6	Dietary supplement: Beta-Hydroxybutyrate as Ca-Mg-salt, active; 24 hour intervention with ketone body supplements additional to a normal diet (isocaloric diet in total) to induce ketosis (exogenous ketone bodies), in a metabolic chamber at physical activity level of 1.6, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.6.; Dietary supplement: ketogenic diet (KetoCal® 4:1 Neutral, Nutricia GmbH, Erlangen, Germany), active; 24 hour interventions with ketogenic isocaloric diet to induce ketosis (endogenous ketone bodies), in a metabolic chamber at physical activity level of 1.6, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.6.; Dietary supplement: fasting, active; 36 hours of fasting, in a metabolic chamber at physical activity level of 1.6, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.6.; Dietary supplement: fasting, inactive; 36 hours of fasting, in a metabolic chamber at physical activity level of 1.3, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.3. The same intervention is reproduced one week later.
Experimental: fasting, inactive; 36 hours fasting, PAL 1.3	Dietary supplement: Beta-Hydroxybutyrate as Ca-Mg-salt, active; 24 hour intervention with ketone body supplements additional to a normal diet (isocaloric diet in total) to induce ketosis (exogenous ketone bodies), in a metabolic chamber at physical activity level of 1.6, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.6.; Dietary supplement: ketogenic diet (KetoCal® 4:1 Neutral, Nutricia GmbH, Erlangen, Germany), active; 24 hour interventions with ketogenic isocaloric diet to induce ketosis (endogenous ketone bodies), in a metabolic chamber at physical activity level of 1.6, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.6.; Dietary supplement: fasting, active; 36 hours of fasting, in a metabolic chamber at physical activity level of 1.6, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.6.; Dietary supplement: fasting, inactive; 36 hours of fasting, in a metabolic chamber at physical activity level of 1.3, after one day of isocaloric diet in a metabolic chamber at physical activity level of 1.3. The same intervention is reproduced one week later.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
appetite control - ghrelin	ghrelin concentration in plasma (24 hour AUC)	24 hours
appetite control - GLP-1 concentration in plasma	Glucose Like Peptide-1 concentration in plasma (24 hour AUC)	24 hours
appetite control - PYY concentration in plasma	Peptide YY concentration in plasma (24 hour AUC)	24 hours
appetite control - subjective feelings of hunger	measured with visual analogue scales (24 hour AUC). The scale consists of a 10 cm vertical line anchored with "not hungry at all" at the left side and with "extremely hungry" at the right side.	24 hours
appetite control - satiety quotient	satiety quotient of standard test-breakfast after 24 hours of intervention	30 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
macronutrient oxidation	measured with indirect calorimetry in a metabolic chamber	24 hours
energy expenditure	measured with indirect calorimetry in a metabolic chamber	24 hours
glycemia - glucose AUC	glucose AUC from continuous glucose monitoring data	24 hours
repeatability of energy expenditure measurements	repeated measurement of 24h-energy expenditure in a metabolic chamber on inactive isocaloric and fasting days	24 hours
ß-Hydroxybutyrate concentration in serum	24 hour ß-Hydroxybutyrate concentration in serum (AUC)	24 hours

Collaborators and Investigators

• Sponsor: University of Kiel

Publications and helpful links

General Publications

• Dorner R, Hagele FA, Koop J, Rising R, Foerster T, Olsen T, Hasler M, Muller MJ, Bosy-Westphal A. Validation of energy expenditure and macronutrient oxidation measured by two new whole-room indirect calorimeters. Obesity (Silver Spring). 2022 Sep;30(9):1796-1805. doi: 10.1002/oby.23527. Epub 2022 Aug 4.

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2020
• Primary Completion (Actual): July 23, 2021
• Study Completion (Actual): July 23, 2021

Study Registration Dates

• First Submitted: July 16, 2020
• First Submitted That Met QC Criteria: July 23, 2020
• First Posted (Actual): July 29, 2020

Study Record Updates

• Last Update Posted (Actual): October 1, 2021
• Last Update Submitted That Met QC Criteria: September 30, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: appetite control; macronutrient oxidation; ketone bodies; metabolic chamber; exogenous ketones
• Other Study ID Numbers: ABW-2020-VK

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No