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).
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)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
45 g whey + 20 g maltodextrin
50 g ketone + 45 g whey + 20 g maltodextrin
Medical Research Labarotory, DoH, Aarhus University Hospital
Aarhus, Denmark
Change in left ventricular outflow tract velocity time integral
Echocardiographic changes in left ventricular outflow tract velocity time integral from the basal period and after 1.5 hours of intervention
Time frame: Measured during the basal period and after 1.5 hours of intervention
Changes in Left Ventricular Ejection Fraction (LVEF)
Echocardiographic changes in LVEF from the basal period and after 1.5 hours of intervention
Time frame: Measured during the basal period and after 1.5 hours of intervention
Changes in Global Longitudinal Strain (GLS)
Echocardiographic changes in GLS from the basal period and after 1.5 hours of intervention
Time frame: Measured during the basal period and after 1.5 hours of intervention
Changes in S´ Max
Echocardiographic changes in S´ Max from the basal period and after 1.5 hours of intervention
Time frame: Measured during the basal period and after 1.5 hours of intervention
Changes in blood pressure
Changes in blood pressure from the basal period and after 1.5 hours of intervention
Time frame: Measured during the basal period and after 1.5 hours of intervention
Changes in heart rate
Changes in heart rate from the basal period and after 1.5 hours of intervention
Time frame: Measured during the basal period and after 1.5 hours of intervention
Changes in axillary temperature
Changes in axillary temperature from the basal period and after 1.5 hours of intervention
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Masking
DOUBLE
Enrollment
8
Time frame: Measured during the basal period and after 1.5 hours of intervention
Difference in Left Ventricular Ejection Fraction (LVEF) (Healthy vs catabolic conditions)
Echocardiographic difference in LVEF during the basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)
Time frame: Measured after 2 hours of basal period
Difference in Global Longitudinal Strain (GLS) (Healthy vs catabolic conditions)
Echocardiographic difference in GLS during the basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)
Time frame: Measured after 2 hours of basal period
Difference in S´ Max (Healthy vs catabolic conditions)
Echocardiographic difference in S´ Max during the basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)
Time frame: Measured after 2 hours of basal period
Difference in axillary temperature (healthy vs catabolic)
Difference in axillary temperature after 2 hours basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)
Time frame: Measured after 2 hours of basal period
Difference in heart rate (healthy vs catabolic)
Difference in heart rate after 2 hours basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)
Time frame: Measured after 2 hours of basal period
Difference in blood pressure (healthy vs catabolic)
Difference in blood pressure after 2 hours basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)
Time frame: Measured after 2 hours of basal period