Endogenous vs. Exogenous Ketone Bodies

Study Overview
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Brief Summary
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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.

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

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

Conditions
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Healthy

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: all subjects are undergoing each intervention
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: fasting, active<br>36 hours fasting, PAL 1.6 | Dietary Supplement: Beta-Hydroxybutyrate as Ca-Mg-salt, active<br>* 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.<br>Dietary Supplement: ketogenic diet (KetoCal® 4:1 Neutral, Nutricia GmbH, Erlangen, Germany), active<br>* 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.<br>Dietary Supplement: fasting, active<br>* 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.<br>Dietary Supplement: fasting, inactive<br>* 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.<br>|
| Experimental: ketogenic diet, active<br>24 hours of ketogenic diet (liquid meals), PAL 1.6 | Dietary Supplement: Beta-Hydroxybutyrate as Ca-Mg-salt, active<br>* 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.<br>Dietary Supplement: ketogenic diet (KetoCal® 4:1 Neutral, Nutricia GmbH, Erlangen, Germany), active<br>* 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.<br>Dietary Supplement: fasting, active<br>* 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.<br>Dietary Supplement: fasting, inactive<br>* 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.<br>|
| Experimental: exogeneous ketone bodies, active<br>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<br>* 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.<br>Dietary Supplement: ketogenic diet (KetoCal® 4:1 Neutral, Nutricia GmbH, Erlangen, Germany), active<br>* 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.<br>Dietary Supplement: fasting, active<br>* 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.<br>Dietary Supplement: fasting, inactive<br>* 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.<br>|
| Experimental: fasting, inactive<br>36 hours fasting, PAL 1.3 | Dietary Supplement: Beta-Hydroxybutyrate as Ca-Mg-salt, active<br>* 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.<br>Dietary Supplement: ketogenic diet (KetoCal® 4:1 Neutral, Nutricia GmbH, Erlangen, Germany), active<br>* 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.<br>Dietary Supplement: fasting, active<br>* 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.<br>Dietary Supplement: fasting, inactive<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ketone bodies, appetite control, macronutrient oxidation, metabolic chamber, exogenous ketones