Anabolic Potential of 3-hydroxybutyrate (3-OHB) and Whey Protein in a Human Catabolic Inflammatory Disease Model

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.

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.

Eligibility Criteria:
Inclusion Criteria:

* Between 20-40 years of age
* Body mass index between 20-30 kg/m\^2
* Healthy
* Oral and written consent forms obtained prior to study day

Exclusion Criteria:

* Recent immobilization of an extremity that is not fully rehabilitated
* Lactose, lidocain or rubber allergies
* Current disease
* Use of anabolic steroids
* Smoking
* Former major abdominal surgery (Or current problems with the GI tract)
* \>10 hours of exercise/weak
* Present ketogenic diets or high-protein diets
* Blood doner that does not want to discontinue blood donations until study completion
* Pending MR scan