Echocardiographic Changes After 3-hydroxy Butyrate+Whey Intake
Condition: Cardiac Output; Endotoxemia; Catabolic State; Echocardiography
MeSH terms: Endotoxemia
Study type: Interventional

Summary: 
      This study evaluates the cardiovascular effects of adding the ketone body 3-hydroxy butyrate
      (3-OHB) to whey protein during human endotoxemia. Further, this study compares cardiovascular
      changes during healthy and catabolic conditions.

      Participants will receive isocaloric, isonitrogenous beverages of either whey or 3-OHB+whey
      in a randomized crossover design during either healthy (overnight fast) or catabolic
      conditions (inflammation/endotoxemia + 36 h fast and bed rest).
    

Detailed description: 
      Background: A newly published study found beneficial cardiovascular effects of 3-OHB infusion
      in a population with chronic heart failure, significantly increasing cardiac output. Similar
      effects on cardiac output were observed in healthy volunteers. These findings pave the way
      for 3-OHB as a therapeutic nutritional supplement, since it is well-absorbed during oral
      consumption. However, it is unknown whether the cardiovascular effects of 3-OHB persist
      during a sepsis-like catabolic state and when administered orally.

      Aim: This study aims to investigate the cardiovascular effects of adding the ketone body
      3-hydroxy butyrate (3-OHB) to whey protein during a human disease model, comprising
      endotoxemia + bed rest + fast.

      Hypothesis:

        1. Adding the ketone body 3-OHB to an oral protein supplement increases cardiac output
           measures

        2. Catabolic stress (endotoxemia/inflammation + 36 h fast and bed rest) induces
           cardiovascular changes compared with healthy conditions (overnight fast)

           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)
    

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: Double (Participant, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Cardiac Output; Endotoxemia; Ketone bodies; 3-hydroxy butyrate; Whey protein; Catabolic State