Echocardiographic Changes After 3-hydroxy Butyrate+Whey Intake

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

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).

Study Overview

• Status: Completed
• Conditions: Endotoxemia; Cardiac Output; Echocardiography; Catabolic State
• Intervention / Treatment: Dietary supplement: Whey; Dietary supplement: 3-OHB + Whey

Detailed Description

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:

1. Adding the ketone body 3-OHB to an oral protein supplement increases cardiac output measures

2. 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)

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

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Medical Research Labarotory, DoH, Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 36 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital Skejby; Arla Food Ingredients, Arla Viby.

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2019
• Primary Completion (Actual): January 23, 2020
• Study Completion (Actual): January 23, 2020

Study Registration Dates

• First Submitted: July 11, 2019
• First Submitted That Met QC Criteria: July 29, 2019
• First Posted (Actual): July 30, 2019

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 9, 2020
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Ketone bodies; Whey protein; Endotoxemia; Cardiac Output; 3-hydroxy butyrate; Catabolic State
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Bacteremia; Toxemia; Endotoxemia
• Other Study ID Numbers: Ketone Heart Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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