Echocardiographic Changes After 3-hydroxy Butyrate+Whey Intake

Study Overview
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Brief Summary
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This study evaluates the cardiovascular effects of adding the ketone body 3-hydroxy butyrate (3-OHB) to whey protein during human endotoxemia. Further, this study compares cardiovascular changes during healthy and catabolic conditions. Participants will receive isocaloric, isonitrogenous beverages of either whey or 3-OHB+whey in a randomized crossover design during either healthy (overnight fast) or catabolic conditions (inflammation/endotoxemia + 36 h fast and bed rest).

Detailed Description
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Background: A newly published study found beneficial cardiovascular effects of 3-OHB infusion in a population with chronic heart failure, significantly increasing cardiac output. Similar effects on cardiac output were observed in healthy volunteers. These findings pave the way for 3-OHB as a therapeutic nutritional supplement, since it is well-absorbed during oral consumption. However, it is unknown whether the cardiovascular effects of 3-OHB persist during a sepsis-like catabolic state and when administered orally. Aim: This study aims to investigate the cardiovascular effects of adding the ketone body 3-hydroxy butyrate (3-OHB) to whey protein during a human disease model, comprising endotoxemia + bed rest + fast. Hypothesis: Adding the ketone body 3-OHB to an oral protein supplement increases cardiac output measures Catabolic stress (endotoxemia/inflammation + 36 h fast and bed rest) induces cardiovascular changes compared with healthy conditions (overnight fast) Interventions: In a randomized crossover design, eight healthy, lean, young men will undergo either: i) Healthy conditions (overnight fast) + whey protein^ ii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest*) + whey protein^ iii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest*) + 3-OHB/whey protein^ *LPS will be administered (1 ng/kg) the day prior to the study together with fast and bed rest. On the study day LPS (0.5 ng/kg) will be injected. ^Beverages will be isonitrogenous and isocaloric (fat will be added) with 45 g whey protein + 20 g maltodextrin. Bolus/sip administration will be applied (1/3 bolus, 1/2 sip)  50 grams of 3-OHB will be orally administered (1/2 bolus, 1/2 sip)

Official Title
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Echocardiographic Changes After Oral Intake of 3-hydroxy Butyrate+Whey in a Human Endotoxemia Model

Conditions
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Cardiac Output, Endotoxemia, Catabolic State, Echocardiography

Intervention / Treatment
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* Dietary Supplement: Whey
* Dietary Supplement: 3-OHB + Whey


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 20-40 years of age Body mass index between 20-30 kg/m^2 Healthy Oral and written consent forms obtained prior to study day Exclusion Criteria: Recent immobilization of an extremity that is not fully rehabilitated Lactose, lidocain or rubber allergies Current disease Use of anabolic steroids Smoking Former major abdominal surgery (Or current problems with the GI tract) •>10 hours of exercise/weak Present ketogenic diets or high-protein diets Blood doner that does not want to discontinue blood donations until study completion Pending MR scan

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

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: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: In a randomized crossover design, eight healthy lean young men will undergo either: i) Healthy conditions (overnight fast) + whey protein ii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest) + whey protein iii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest) + 3-OHB/whey protein
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy + Whey<br>Healthy conditions (overnight fast) | Dietary Supplement: Whey<br>* 45 g whey + 20 g maltodextrin<br>|
| Experimental: Catabolic + Whey<br>Catabolic conditions (36-hour fast, bed rest and inflammation (LPS)) | Dietary Supplement: Whey<br>* 45 g whey + 20 g maltodextrin<br>|
| Experimental: Catabolic + 3-OHB / Whey<br>Catabolic conditions (36-hour fast, bed rest and inflammation (LPS)) | Dietary Supplement: 3-OHB + Whey<br>* 50 g ketone + 45 g whey + 20 g maltodextrin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular outflow tract velocity time integral | Echocardiographic changes in left ventricular outflow tract velocity time integral from the basal period and after 1.5 hours of intervention | Measured during the basal period and after 1.5 hours of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Left Ventricular Ejection Fraction (LVEF) | Echocardiographic changes in LVEF from the basal period and after 1.5 hours of intervention | Measured during the basal period and after 1.5 hours of intervention | 
| Changes in Global Longitudinal Strain (GLS) | Echocardiographic changes in GLS from the basal period and after 1.5 hours of intervention | Measured during the basal period and after 1.5 hours of intervention | 
| Changes in S´ Max | Echocardiographic changes in S´ Max from the basal period and after 1.5 hours of intervention | Measured during the basal period and after 1.5 hours of intervention | 
| Changes in blood pressure | Changes in blood pressure from the basal period and after 1.5 hours of intervention | Measured during the basal period and after 1.5 hours of intervention | 
| Changes in heart rate | Changes in heart rate from the basal period and after 1.5 hours of intervention | Measured during the basal period and after 1.5 hours of intervention | 
| Changes in axillary temperature | Changes in axillary temperature from the basal period and after 1.5 hours of intervention | Measured during the basal period and after 1.5 hours of intervention | 
| Difference in Left Ventricular Ejection Fraction (LVEF) (Healthy vs catabolic conditions) | Echocardiographic difference in LVEF during the basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure) | Measured after 2 hours of basal period | 
| Difference in Global Longitudinal Strain (GLS) (Healthy vs catabolic conditions) | Echocardiographic difference in GLS during the basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure) | Measured after 2 hours of basal period | 
| Difference in S´ Max (Healthy vs catabolic conditions) | Echocardiographic difference in S´ Max during the basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure) | Measured after 2 hours of basal period | 
| Difference in axillary temperature (healthy vs catabolic) | Difference in axillary temperature after 2 hours basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure) | Measured after 2 hours of basal period | 
| Difference in heart rate (healthy vs catabolic) | Difference in heart rate after 2 hours basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure) | Measured after 2 hours of basal period | 
| Difference in blood pressure (healthy vs catabolic) | Difference in blood pressure after 2 hours basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure) | Measured after 2 hours of basal period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac Output, Endotoxemia, Ketone bodies, 3-hydroxy butyrate, Whey protein, Catabolic State