Endogenous vs. Exogenous Ketone Bodies

• Sponsor: University of Kiel (Other)
• Overall Status: Completed
• CT.gov ID: NCT04490226
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arms: 4
• Actual Duration (Months): 11
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	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	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: all subjects are undergoing each interventionall subjects are undergoing each intervention
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Impact of Endogenous vs. Exogenous Ketone Bodies on Appetite Control and Macronutrient Oxidation
• Actual Study Start Date: Aug 21, 2020
• Actual Primary Completion Date: Jul 23, 2021
• Actual Study Completion Date: Jul 23, 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. appetite control - ghrelin [24 hours]

   ghrelin concentration in plasma (24 hour AUC)

2. appetite control - GLP-1 concentration in plasma [24 hours]

   Glucose Like Peptide-1 concentration in plasma (24 hour AUC)

3. appetite control - PYY concentration in plasma [24 hours]

   Peptide YY concentration in plasma (24 hour AUC)

4. appetite control - subjective feelings of hunger [24 hours]

   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.

5. appetite control - satiety quotient [30 min]

   satiety quotient of standard test-breakfast after 24 hours of intervention

Secondary Outcome Measures

1. macronutrient oxidation [24 hours]

   measured with indirect calorimetry in a metabolic chamber

2. energy expenditure [24 hours]

   measured with indirect calorimetry in a metabolic chamber

3. glycemia - glucose AUC [24 hours]

   glucose AUC from continuous glucose monitoring data

4. repeatability of energy expenditure measurements [24 hours]

   repeated measurement of 24h-energy expenditure in a metabolic chamber on inactive isocaloric and fasting days

5. ß-Hydroxybutyrate concentration in serum [24 hours]

   24 hour ß-Hydroxybutyrate concentration in serum (AUC)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 35 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institute of Human Nutrition	Kiel		Germany	24105

Sponsors and Collaborators

• University of Kiel

Investigators

• Principal Investigator: Anja Bosy-Westphal, PhD, MD, Institute of Human Nutrition, Kiel University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Prof. Dr. Dr. Anja Bosy-Westphal, Prof. Anja Bosy-Westphal, PhD, MD, University of Kiel
• ClinicalTrials.gov Identifier: NCT04490226
• Other Study ID Numbers: ABW-2020-VK
• First Posted: Jul 29, 2020
• Last Update Posted: Oct 1, 2021
• Last Verified: Sep 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Prof. Dr. Dr. Anja Bosy-Westphal, Prof. Anja Bosy-Westphal, PhD, MD, University of Kiel: ketone bodies; appetite control; macronutrient oxidation; metabolic chamber; exogenous ketones

Study Results

No Results Posted as of Oct 1, 2021