Whey vs Casein to Combat Post-inflammatory Protein and Muscle Waste in Acute Disease

Nutrition Clinical Trial

Official title:

Whey vs Casein to Combat Post-inflammatory Protein and Muscle Waste - Combining Endotoxemia, Immobilisation and Fasting in Healthy Young Males in a New Model of Acute Febrile Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03319550
• Other study ID #: theproteinstudy
• Status: Completed
• Phase: N/A
• Start date: December 7, 2017
• Est. completion date: September 19, 2018

Study information

• Verified date: November 2018
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study compares three different protein supplements (casein, whey and leucine-enriched whey) and their effect on post-inflammatory muscle waste in a model of acute disease. Each test person will undergo all three interventions.

It is believed that leucine is the primary driver of muscle protein synthesis and therefore we hypothesize that leucine-enriched whey and whey are superior to casein in combating post-inflammatory muscle waste, because of its higher leucine content (16%, 11% and 9% leucine, respectively).

Description:

Background:

Acute illness is accompanied by infection/inflammation, anorexia and immobilization all contributing to muscle loss, making nutritional supplement optimization an obvious target for investigation and eventually clinical intervention. In the clinical setting large heterogenicity among patients complicates investigations of muscle metabolism during acute illness. Therefore we introduce a disease model by combining "Inflammation + 36 hour fast and bedrest". Inflammation/febrile illness will be initiated by using the well-established "human endotoxemia model" with a bolus injection of Escherichia coli lipopolysaccharide (LPS), known to cause inflammation comparable with the initial phase of sepsis. The amino acid leucine has shown to be particularly anabolic in performance sports, but little is known about its potential beneficial effects during acute illness. Leucine is a powerful activator of muscle protein synthesis and it seems that protein supplements with the highest leucine content elicit a greater increase in protein synthesis than those with a smaller fraction of leucine.

The protein supplements used most in hospitals contain casein derived protein, which has a much lower leucine content than the whey protein compounds typically used in performance sports.

This study compares three different protein supplements.The study is an open, randomized crossover trial. Laboratory technicians, test subjects and investigators will be blinded.

Interventions:

I. LPS (1 ng/kg as bolus) + 36 h fasting + 36 h bedrest + Casein (9% leucine) II. LPS (1 ng/kg as bolus) + 36 h fasting + 36 h bedrest + Whey (11% leucine) III. LPS (1 ng/kg as bolus) + 36 h fasting + 36 h bedrest + Leucine-enriched whey (16% leucine)

The test objects will be given 0,6 g protein/kg, 1/3 as a bolus and 2/3 as sipping over a period of 3,5 hour. Muscle metabolism will be investigated by phenylalanine tracer using the forearm model and total protein metabolism using a carbamide tracer. Through muscle biopsies intracellular signalling pathways will be investigated.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 19, 2018
• Est. primary completion date: September 19, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 40 Years

Eligibility

Inclusion Criteria:

• Healthy Male

• Age between 20-40

• BMI between 20-30

• Normal health examination and blood samples

• Written informed consent

Exclusion Criteria:

• Immobilisation of an extremity, unless a doctor has declared it fully rehabilitated.

• Allergy against lidocain or latex.

• The use of anabolic steroids

• Disease like: Diabetes, epilepsia, infection, cardiovascular disease.

Related Conditions & MeSH terms

• Casein
• Endotoxemia
• Metabolism
• Milk Protein
• Muscle Protein Synthesis
• Nutrition
• Whey

Intervention

Dietary Supplement:
• Casein
see experimental description
• Whey
see experimental description
• Leucine-enriched whey
see experimental description

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Arla Food for Health

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in muscle phenylalanine netbalance over the forearm muscle	Changes of muscle phenylalanine net balance (= arterio(phe conc)-venous(phe conc) x flow) from baseline to 3.5 hours after intervention using the forearm model	Change from baseline to 3.5 hours after intervention
Secondary	Change in whole body protein metabolism measured by a combination of phenylalanine- and tyrosine tracer	Changes in whole body protein synthesis rates (umol/kg/h), breakdown rates (umol/kg/h), phenylalanine to tyrosine conversion rates (umol/kg/h) and net balance (umol/kg/h)	Change from baseline to 3.5 hours after intervention
Secondary	Blood enrichment of essential amino acids	measures of essential amino acids in the blood	At baseline and every 30 minutes during the intervention period (3.5 hours)
Secondary	Changes in insulin concentrations	Measures of insulin concentration in blood	At baseline and every 30 minutes during the intervention period (3.5 hours)
Secondary	Change in Intracellular signalling in muscle measured by western blotting.	Investigating intracellular activity of muscle metabolism pathways by western blotting.	Change from baseline and after 2 hours of intervention
Secondary	Energy expenditure	Using indirect calorimetry for 15 min	At baseline and after 2.5 hours of intervention
Secondary	Changes in Glucose, fat and protein oxidation rates	Using indirect calorimetry for 15 min for measuring glucose- (mg/kg/min), fat- (mg/kg/min) and protein oxidation (mg/kg/min)	At baseline and after 2.5 hours of intervention
Secondary	Change in muscle breakdown and synthesis rates measured by phenylalanine tracer	changes from baseline to 3.5 hours after intervention in Ra(phe)=breakdown (umol/kg/h) and Rd(phe)=synthesis rate (umol/kg/h)	Change from baseline to 3.5 hours after intervention
Secondary	Changes in Glucagon concentrations	Glucagon concentrations in blood	Change from baseline and to 1 hour and 3.5 hour after the intervention
Secondary	Changes in GIP concentrations	GIP concentrations in blood	Change from baseline and to 1 hour and 3.5 hour after the intervention
Secondary	Changes in GLP-1 concentrations	GLP-1 concentrations in blood	Change from baseline and to 1 hour and 3.5 hour after the intervention
Secondary	Changes in Glucose concentrations	Glucose concentrations in blood	At baseline and every 30 minutes during the intervention period (3.5 hours)
Secondary	Changes in heart rate profile upon repeated LPS exposure	heart rate (beats/min)	Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)
Secondary	Changes in temperature profile upon repeated LPS exposure	Axillary temperature (celcius)	Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)
Secondary	Changes in blood pressure profile upon repeated LPS exposure	blood pressure (mmHg)	Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)
Secondary	Changes in symptom score profile upon repeated LPS exposure	symptom score (from 0-5) for nausea, back pain, muscle pain, headache and chills. 0=no symptoms, 5=severe symptoms.	Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)
Secondary	Changes in TNfalfa profile upon repeated LPS exposure	TNfalfa blood concentrations	Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)
Secondary	Changes in IL-1 profile upon repeated LPS exposure	IL-1 blood concentrations	Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)
Secondary	Changes in IL-6 profile upon repeated LPS exposure	IL-6 blood concentrations	Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)
Secondary	Changes in IL-10 profile upon repeated LPS exposure	IL-10 blood concentrations	Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)