Whey vs Casein to Combat Post-inflammatory Protein and Muscle Waste in Acute Disease
Study Details
Study Description
Brief 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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed 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:
- 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Casein "LPS + 36 hour fast and bedrest" + Casein (9% leucine) - 0.6 g protein/kg bodyweight, 1/3 as bolus and 2/3 as sipping. |
Dietary Supplement: Casein
see experimental description
|
| Experimental: Whey "LPS + 36 hour fast and bedrest" + Whey (11% leucine) - 0.6 g protein/kg bodyweight, 1/3 as bolus and 2/3 as sipping |
Dietary Supplement: Whey
see experimental description
|
| Experimental: Leucine-enriched whey "LPS + 36 hour fast and bedrest" + Leucine-enriched whey (16% leucine) - 0.6 g protein/kg bodyweight, 1/3 as bolus and 2/3 as sipping |
Dietary Supplement: Leucine-enriched whey
see experimental description
|
Outcome Measures
Primary Outcome Measures
- Change in muscle phenylalanine netbalance over the forearm muscle [Change from baseline to 3.5 hours after intervention]
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
Secondary Outcome Measures
- Change in whole body protein metabolism measured by a combination of phenylalanine- and tyrosine tracer [Change from baseline to 3.5 hours after intervention]
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)
- Blood enrichment of essential amino acids [At baseline and every 30 minutes during the intervention period (3.5 hours)]
measures of essential amino acids in the blood
- Changes in insulin concentrations [At baseline and every 30 minutes during the intervention period (3.5 hours)]
Measures of insulin concentration in blood
- Change in Intracellular signalling in muscle measured by western blotting. [Change from baseline and after 2 hours of intervention]
Investigating intracellular activity of muscle metabolism pathways by western blotting.
- Energy expenditure [At baseline and after 2.5 hours of intervention]
Using indirect calorimetry for 15 min
- Changes in Glucose, fat and protein oxidation rates [At baseline and after 2.5 hours of intervention]
Using indirect calorimetry for 15 min for measuring glucose- (mg/kg/min), fat- (mg/kg/min) and protein oxidation (mg/kg/min)
- Change in muscle breakdown and synthesis rates measured by phenylalanine tracer [Change from baseline to 3.5 hours after intervention]
changes from baseline to 3.5 hours after intervention in Ra(phe)=breakdown (umol/kg/h) and Rd(phe)=synthesis rate (umol/kg/h)
- Changes in Glucagon concentrations [Change from baseline and to 1 hour and 3.5 hour after the intervention]
Glucagon concentrations in blood
- Changes in GIP concentrations [Change from baseline and to 1 hour and 3.5 hour after the intervention]
GIP concentrations in blood
- Changes in GLP-1 concentrations [Change from baseline and to 1 hour and 3.5 hour after the intervention]
GLP-1 concentrations in blood
- Changes in Glucose concentrations [At baseline and every 30 minutes during the intervention period (3.5 hours)]
Glucose concentrations in blood
- Changes in heart rate profile upon repeated LPS exposure [Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)]
heart rate (beats/min)
- Changes in temperature profile upon repeated LPS exposure [Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)]
Axillary temperature (celcius)
- Changes in blood pressure profile upon repeated LPS exposure [Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)]
blood pressure (mmHg)
- Changes in symptom score profile upon repeated LPS exposure [Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)]
symptom score (from 0-5) for nausea, back pain, muscle pain, headache and chills. 0=no symptoms, 5=severe symptoms.
- Changes in TNfalfa profile upon repeated LPS exposure [Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)]
TNfalfa blood concentrations
- Changes in IL-1 profile upon repeated LPS exposure [Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)]
IL-1 blood concentrations
- Changes in IL-6 profile upon repeated LPS exposure [Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)]
IL-6 blood concentrations
- Changes in IL-10 profile upon repeated LPS exposure [Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)]
IL-10 blood concentrations
Eligibility Criteria
Criteria
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.
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The use of anabolic steroids
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Disease like: Diabetes, epilepsia, infection, cardiovascular disease.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Aarhus University Hospital | Aarhus | Denmark | 8000 |
Sponsors and Collaborators
- University of Aarhus
- Arla Food for Health
Investigators
- Principal Investigator: Niels Moeller, Professor, Institute for clinical Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- theproteinstudy