Whey vs Casein to Combat Post-inflammatory Protein and Muscle Waste in Acute Disease
Condition: Muscle Protein Synthesis; Endotoxemia; Nutrition; Milk Protein; Metabolism; Whey; Casein
MeSH terms: Endotoxemia
Study type: Interventional

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).
    

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:

      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.
    

Intervention name(s): Casein; Whey; Leucine-enriched whey
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): see experimental description; see experimental description; see experimental description
Intervention MeSH terms: Caseins
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: 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.
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: milk protein, endotoxemia, muscle protein synthesis, whey, casein