Anabolic Potential of 3-hydroxybutyrate (3-OHB) and Whey Protein in a Human Catabolic Inflammatory Disease Model

June 9, 2020 updated by: University of Aarhus

Anabolic Potential of Adding 3-hydroxybutyrate (3-OHB) to Whey Protein in a Catabolic Inflammatory Disease Model: A Human Randomized Controlled Trial

This study aims to investigate the muscle anabolic potential of adding ketone (3-hydroxybutyrate) to whey protein compared with isocaloric, isonitrogenous whey protein in a human model of inflammatory catabolic disease. Further, this study aims to investigate whether the same amount of whey protein has different effects on muscles in an catabolic inflammatory setting compared with a healthy setting.

Study Overview

Detailed Description

Background: Muscle wasting during hospitalization is caused by a combination of immobilization (bed rest), hypocaloric diet and inflammation (e.g. sepsis), and preventive measures are needed. Whey protein is particularly potent in inducing muscle protein synthesis compared with other proteins, at least in healthy populations. Further, the ketone body 3-hydroxybutyrate (3-OHB) effectively preserved muscle in a model of acute inflammatory disease. However, little is known about whether 3-OHB can potentiate the effects of whey protein in a catabolic inflammatory setting.

Aim: This study aims to investigate the muscle anabolic potential of adding ketone (3-OHB) to whey protein compared with isocaloric, isonitrogenous whey protein in a human model of catabolic inflammatory disease. Further, this study aims to investigate whether the same amount of whey protein has different effects on muscles in an catabolic inflammatory setting compared with a healthy setting.

Hypothesis:

  1. 3-OHB potentiates the effect of whey protein in maintaining muscle mass in a catabolic inflammatory setting.
  2. The same amount of whey protein will have decreased muscle anabolic effects during catabolic inflammatory conditions compared with healthy conditions

    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)

    Before each study day:

    The participants arrive fasting (only tap water allowed) by taxi on the study days. They have been without febrile disease the week prior to investigation, and have not performed exercise for 24 hours.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Aarhus, Denmark, 8000
        • Medical Research Laboratory, DoH, Aarhus University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Healthy + Whey
Healthy conditions (overnight fast)
45 g whey + 20 g maltodextrin
Experimental: Catabolic + Whey
Catabolic conditions (36-hour fast, bed rest and inflammation (LPS))
45 g whey + 20 g maltodextrin
Experimental: Catabolic + 3-OHB / Whey
Catabolic conditions (36-hour fast, bed rest and inflammation (LPS))
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 forearm muscle kinetics measured by phenylalanine tracer (Netbalance, rate of disappearence and rate of apperance of phenylanine, nmol/100ml muscle/min)
Time Frame: Change from baseline to 3.5 hours after intervention
Changes of forearm muscle phenylalanine kinetics from baseline to 3.5 hours after intervention using the forearm model
Change from baseline to 3.5 hours after intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in concentration of total aminoacids
Time Frame: Change from baseline to 3.5 hours after intervention
Change in total aminoacids from baseline to the end of the 3.5 hour sipping period
Change from baseline to 3.5 hours after intervention
Change in concentration of 3-hydroxybutyrate (mmol/L) )
Time Frame: Measured at baseline and every 30. min throughout the 3.5 hour sipping period
Change in blood BHB levels from baseline to the end of the 3.5 hour sipping period (iAUC)
Measured at baseline and every 30. min throughout the 3.5 hour sipping period
Change in glucose kinetics measured by glucose tracer (rate of apperance and rate of disappearance, mg/kg/min)
Time Frame: Change from baseline to 3.5 hours after intervention
Change in glucose kinetics from baseline to to the end of the 3.5 hour sipping period
Change from baseline to 3.5 hours after intervention
Change in concentration of plasma insulin
Time Frame: Measured at baseline and every 30. min throughout the 3.5 hour sipping period
Change in plasma insulin levels from baseline to the end of the 3.5 hour sipping period (iAUC)
Measured at baseline and every 30. min throughout the 3.5 hour sipping period
Change in concentration of plasma glucose
Time Frame: Measured at baseline and every 30. min throughout the 3.5 hour sipping period
Change in glucose levels from baseline and after 3.5 hour sipping period expressed as iAUC.
Measured at baseline and every 30. min throughout the 3.5 hour sipping period
Change in concentration of free fatty acids (FFA) levels
Time Frame: Change from baseline to 3.5 hours after intervention
Change in FFA from baseline to the end of the sipping period
Change from baseline to 3.5 hours after intervention
Change in concentration of C-reactive peptide (CRP)
Time Frame: Change from baseline to 3.5 hours after intervention
Change in CRP from baseline to the end of the sipping period
Change from baseline to 3.5 hours after intervention
Change in concentration of blood leucocytes (x10^9/L)
Time Frame: Change from baseline to 3.5 hours after intervention
Change in leucocytes from baseline to the end of the sipping period
Change from baseline to 3.5 hours after intervention
Change in concentration of stress hormones (glucagon, cortisol, adrenalin, noradrenalin)
Time Frame: Change from baseline to 3.5 hours after intervention
Change in hormones from baseline and after 3.5 hour sipping period
Change from baseline to 3.5 hours after intervention
Change in intracellular muscle signalling
Time Frame: Change from baseline to 3.5 hours after intervention
Change in muscle signalling in muscle biopsies by western blot from baseline to the sipping period
Change from baseline to 3.5 hours after intervention
Difference in muscle forearm kinetics measured by phenylalanine tracer (Netbalance, rate of apperance, rate og disappearance) (healthy vs catabolic)
Time Frame: measured at the end of the 3.5 hour basal period
Phenylalanine forearm kinetics measured by phenylalanine tracer at the end of the 3.5 hour basal period in healthy vs catabolic (pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)
measured at the end of the 3.5 hour basal period
Difference in concentration of total amino acids (healthy vs catabolic)
Time Frame: measured at the end of the 3.5 hour basal period
Total amino acids measured at the end of the 3.5 hour basal period in healthy vs catabolic conditions (pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)
measured at the end of the 3.5 hour basal period
Difference in glucose kinetics measured with glucose tracer (mg/kg/min) (healthy vs catabolic)
Time Frame: measured at the end of the 3.5 hour basal period
Glucose kinetics measured by glucose tracer at the end of the 3.5 hour basal period in healthy vs catabolic conditions (pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)
measured at the end of the 3.5 hour basal period
Difference in concentration of free fatty acids (FFA) (healthy vs catabolic)
Time Frame: Measured at the end of the 3.5 hour basal period.
FFA measured at the end of the basal period in healthy vs catabolic (pooled mean of the two catabolic days)
Measured at the end of the 3.5 hour basal period.
Difference in concentration of C-reactive peptide (CRP) (healthy vs catabolic)
Time Frame: Measured at the end of the 3.5 hour basal period.
CRP measured at the end of the basal period in healthy vs catabolic (pooled mean of the two catabolic days)
Measured at the end of the 3.5 hour basal period.
Difference in concentration of leucocytes (healthy vs catabolic)
Time Frame: Measured at the end of the 3.5 hour basal period.
Leucocytes measured at the end of the basal period in healthy vs catabolic (pooled mean of the two catabolic days)
Measured at the end of the 3.5 hour basal period.
Difference in intracellular muscle signalling (healthy vs catabolic)
Time Frame: Measured at the end of the 3.5 hour basal period.
Muscle signalling measured in muscle biopsies by western blot during the 3.5 hour basal period in healthy vs catabolic (pooled mean of the two catabolic days)
Measured at the end of the 3.5 hour basal period.
Difference in concentration of 3-hydroxybutyrate (mmol/L) (healthy vs catabolic)
Time Frame: Measured at the end of the 3.5 hour basal period.
3-hydroxybutyrate measured at the end of the basal period in healthy vs catabolic (pooled mean of the two catabolic days)
Measured at the end of the 3.5 hour basal period.
Difference in concentration of hormones (insulin, glucagon, cortisol, growth hormone, adrenaline, noradrenalin) (healthy vs catabolic)
Time Frame: Measured at the end of the 3.5 hour basal period.
Hormones (insulin, glucagon, cortisol, growth hormone, adrenaline, noradrenalin) measured at the end of the basal period in healthy vs catabolic (pooled mean of the two catabolic days)
Measured at the end of the 3.5 hour basal period.
Difference in whole body protein metabolism (healthy vs catabolic)
Time Frame: Measured at the end of the 3.5 hour basal period.
Difference in whole body protein metabolism measured with tyrosine tracers at the end of the basal period in healthy vs catabolic (pooled mean of the two catabolic days)
Measured at the end of the 3.5 hour basal period.
Difference in concentration of cytokines (healthy vs catabolic)
Time Frame: Measured at baseline and 120 and 240 minutes after LPS administration
Cytokines (TNFalfa, IL-10, IL-6 and IL-1beta) measured between healthy and catabolic conditions (iAUC, a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure))
Measured at baseline and 120 and 240 minutes after LPS administration
Difference in axillary temperature (healthy vs catabolic)
Time Frame: Measured at baseline and 1, 2, 3, 4, 5, 6 and 7 hours after LPS administration
Change in axillary temperature (iAUC). A pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure.
Measured at baseline and 1, 2, 3, 4, 5, 6 and 7 hours after LPS administration
Difference in heart rate (healthy vs catabolic)
Time Frame: Measured at baseline and 1, 2, 3, 4, 5, 6 and 7 hours after LPS administration
Change in heart rate (iAUC). A pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure.
Measured at baseline and 1, 2, 3, 4, 5, 6 and 7 hours after LPS administration
Difference in mean arterial pressure (MAP) (healthy vs catabolic)
Time Frame: Measured at baseline and 1, 2, 3, 4, 5, 6 and 7 hours after LPS administration
Change in MAP (iAUC). A pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure.
Measured at baseline and 1, 2, 3, 4, 5, 6 and 7 hours after LPS administration
Difference in symptom score (healthy vs catabolic)
Time Frame: Measured at baseline and 1, 2, 3, 4, 5, 6 and 7 hours after LPS administration
Change from baseline and throughout the experiment (iAUC). A pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure. Scale 0-5, 0=no symptoms and 5=severe symptoms
Measured at baseline and 1, 2, 3, 4, 5, 6 and 7 hours after LPS administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Niels Moeller, Professor, Aarhus University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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

August 19, 2019

First Posted (Actual)

August 21, 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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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