Echocardiographic Changes After 3-hydroxy Butyrate+Whey Intake

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:

• Adding the ketone body 3-OHB to an oral protein supplement increases cardiac output measures
• 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)

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