Anabolic Potential of 3-hydroxybutyrate (3-OHB) and Whey Protein in a Human Catabolic Inflammatory Disease Model
Condition: Endotoxemia; Muscle Loss; Catabolic State; Protein; Disease; Nutrition Therapy
MeSH terms: Endotoxemia
Study type: Interventional

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.
    

Detailed 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.
    

Intervention name(s): Whey; 3-OHB + Whey
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 45 g whey + 20 g maltodextrin; 50 g ketone + 45 g whey + 20 g maltodextrin
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: 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
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: endotoxemia; muscle loss; catabolic state; whey protein; 3-hydroxy butyrate