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| Name | Class |
|---|---|
| Arla Foods | INDUSTRY |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Casein | Experimental | "LPS + 36 hour fast and bedrest" + Casein (9% leucine) - 0.6 g protein/kg bodyweight, 1/3 as bolus and 2/3 as sipping. |
|
| Whey | Experimental | "LPS + 36 hour fast and bedrest" + Whey (11% leucine) - 0.6 g protein/kg bodyweight, 1/3 as bolus and 2/3 as sipping |
|
| Leucine-enriched whey | Experimental | "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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Casein | Dietary Supplement | see experimental description |
| |
| Whey |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Niels Moeller, Professor | Institute for clinical Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aarhus University Hospital | Aarhus | 8000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33693737 | Derived | Mose M, Moller N, Jessen N, Mikkelsen UR, Christensen B, Rakvaag E, Hartmann B, Holst JJ, Jorgensen JOL, Rittig N. beta-Lactoglobulin Is Insulinotropic Compared with Casein and Whey Protein Ingestion during Catabolic Conditions in Men in a Double-Blinded Randomized Crossover Trial. J Nutr. 2021 Jun 1;151(6):1462-1472. doi: 10.1093/jn/nxab010. |
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We will analyse all data ourselves
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| ID | Term |
|---|---|
| D019446 | Endotoxemia |
| ID | Term |
|---|---|
| D016470 | Bacteremia |
| D018805 | Sepsis |
| D007239 | Infections |
| D014115 | Toxemia |
| D018746 |
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| ID | Term |
|---|---|
| D002364 | Caseins |
| D000067796 | Whey |
| ID | Term |
|---|---|
| D008894 | Milk Proteins |
| D000080224 | Animal Proteins, Dietary |
| D004044 | Dietary Proteins |
| D011506 | Proteins |
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Interventions*:
I. LPS (1 ng/kg as bolus) + 36 h fasting + 36 h bedrest + Casein
II. LPS (1 ng/kg as bolus) + 36 h fasting + 36 h bedrest + Whey
III. LPS (1 ng/kg as bolus) + 36 h fasting + 36 h bedrest + Leucine-enriched whey
* LPS will be administered on study day 1 and measurements of metabolism will be performed on study day 2 where we see the secondary effects of acute inflammation. The patient will stay at the hospital over night to ensure continues fast and bedrest.
The beverages will be isocaloric and with the same total protein content. The basal period will be 2,5 hour with infusion of tracer. Hereafter a total amount of 0,6 g protein/kg bodyweight will be orally administered, 1/3 as a bolus and 2/3 as sipping over 3,5 hours. Muscle biopsies and blodsampels will be collected during both the basal and the sipping period.
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The three different protein supplements will be fabricated with the same taste, colour and weight. They will be named "A", "B" and "C" and the investigator will not know which protein is which until all data has been collected and analysed.
| Dietary Supplement |
see experimental description |
|
| Leucine-enriched whey | Dietary Supplement | see experimental description |
|
| 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) |
| Changes in insulin concentrations | Measures of insulin concentration in blood | At baseline and every 30 minutes during the intervention period (3.5 hours) |
| 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 |
| Energy expenditure | Using indirect calorimetry for 15 min | At baseline and after 2.5 hours of intervention |
| 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 |
| 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 |
| Changes in Glucagon concentrations | Glucagon concentrations in blood | Change from baseline and to 1 hour and 3.5 hour after the intervention |
| Changes in GIP concentrations | GIP concentrations in blood | Change from baseline and to 1 hour and 3.5 hour after the intervention |
| Changes in GLP-1 concentrations | GLP-1 concentrations in blood | Change from baseline and to 1 hour and 3.5 hour after the intervention |
| Changes in Glucose concentrations | Glucose concentrations in blood | At baseline and every 30 minutes during the intervention period (3.5 hours) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000602 |
| Amino Acids, Peptides, and Proteins |
| D010750 | Phosphoproteins |
| D008892 | Milk |
| D001628 | Beverages |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D003611 | Dairy Products |
| D005502 | Food |
| D019602 | Food and Beverages |