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

Muscle Loss Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04064268
• Other study ID #: Ketone Study
• Status: Completed
• Phase: N/A
• Start date: June 17, 2019
• Est. completion date: January 23, 2020

Study information

• Verified date: July 2019
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: January 23, 2020
• Est. primary completion date: January 23, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Catabolic State
• Endotoxemia
• Muscle Loss
• Nutrition Therapy
• Protein; Disease

Intervention

Dietary Supplement:
• Whey
45 g whey + 20 g maltodextrin
• 3-OHB + Whey
50 g ketone + 45 g whey + 20 g maltodextrin

Locations

Country	Name	City	State
Denmark	Medical Research Laboratory, DoH, Aarhus University Hospital	Aarhus

Sponsors (3)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital, Arla Foods Ingredients

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in forearm muscle kinetics measured by phenylalanine tracer (Netbalance, rate of disappearence and rate of apperance of phenylanine, nmol/100ml muscle/min)	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	Change in concentration of total aminoacids	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
Secondary	Change in concentration of 3-hydroxybutyrate (mmol/L) )	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
Secondary	Change in glucose kinetics measured by glucose tracer (rate of apperance and rate of disappearance, mg/kg/min)	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
Secondary	Change in concentration of plasma insulin	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
Secondary	Change in concentration of plasma glucose	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
Secondary	Change in concentration of free fatty acids (FFA) levels	Change in FFA from baseline to the end of the sipping period	Change from baseline to 3.5 hours after intervention
Secondary	Change in concentration of C-reactive peptide (CRP)	Change in CRP from baseline to the end of the sipping period	Change from baseline to 3.5 hours after intervention
Secondary	Change in concentration of blood leucocytes (x10^9/L)	Change in leucocytes from baseline to the end of the sipping period	Change from baseline to 3.5 hours after intervention
Secondary	Change in concentration of stress hormones (glucagon, cortisol, adrenalin, noradrenalin)	Change in hormones from baseline and after 3.5 hour sipping period	Change from baseline to 3.5 hours after intervention
Secondary	Change in intracellular muscle signalling	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
Secondary	Difference in muscle forearm kinetics measured by phenylalanine tracer (Netbalance, rate of apperance, rate og disappearance) (healthy vs catabolic)	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
Secondary	Difference in concentration of total amino acids (healthy vs catabolic)	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
Secondary	Difference in glucose kinetics measured with glucose tracer (mg/kg/min) (healthy vs catabolic)	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
Secondary	Difference in concentration of free fatty acids (FFA) (healthy vs catabolic)	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.
Secondary	Difference in concentration of C-reactive peptide (CRP) (healthy vs catabolic)	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.
Secondary	Difference in concentration of leucocytes (healthy vs catabolic)	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.
Secondary	Difference in intracellular muscle signalling (healthy vs catabolic)	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.
Secondary	Difference in concentration of 3-hydroxybutyrate (mmol/L) (healthy vs catabolic)	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.
Secondary	Difference in concentration of hormones (insulin, glucagon, cortisol, growth hormone, adrenaline, noradrenalin) (healthy vs catabolic)	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.
Secondary	Difference in whole body protein metabolism (healthy vs catabolic)	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.
Secondary	Difference in concentration of cytokines (healthy vs catabolic)	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
Secondary	Difference in axillary temperature (healthy vs catabolic)	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
Secondary	Difference in heart rate (healthy vs catabolic)	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
Secondary	Difference in mean arterial pressure (MAP) (healthy vs catabolic)	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
Secondary	Difference in symptom score (healthy vs catabolic)	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