1350508 - A CMR Investigation Of Acute Exogenous Ketosis: Cardiac Function And Myocardial Blood Flow Response Following Ketone Ester Ingestion

Healthy adults typically meet 60% to 90% of the energy needs of the heart by fatty acid oxidation; however, cardiomyocytes are responsive to changes in substrate availability, and the heart uses ketones as fuel in relation to circulating concentrations. Infusion of the ketone body beta-hydroxybutyrate (BHB) to raise circulating [BHB] into the range achievable via a ketogenic diet (0.5 to 5.0 mM) has been shown to increase resting cardiac output in heart failure patients [1] and to increase myocardial blood flow (MBF) in healthy elderly adults [2], while decreasing myocardial glucose uptake.

Oral ingestion of ketone esters (KE) is a practical method of increasing [BHB], and KE products are marketed as nutritional supplements [3]. KE ingestion has been shown to increase [BHB] for hours, and elicits similar cardiovascular effects as BHB infusion [4]. However, MBF has not been assessed following KE ingestion. We used cardiovascular magnetic resonance (CMR) to assess changes in cardiac function and MBF to evaluate the acute cardiovascular effects of KE ingestion in healthy adults.

 

Methods:

Ten healthy adult subjects (Table 1) were enrolled. Subjects were hydrated,  abstained from caffeine, and fasted overnight prior to the experiment. Images were acquired on a 3T scanner (MAGNETOM Vida, Siemens Healthcare, Germany). At baseline we weighed the subjects, obtained venous blood to measure [BHB] and [glucose], acquired a full set of cine images to evaluate baseline function, and measured MBF using a prototype quantitative first-pass perfusion sequence [5]. Subjects then consumed a 50g KE drink within a 10min period, and underwent repeated cine imaging and blood draws every 15-30min. At 120min post KE ingestion, a second perfusion scan was run to evaluate the impact of BHB on MBF.

Cardiac function was analyzed using SuiteHeart (Neosoft LLC, Pewaukee, WI). Changes in function were statistically analysed using 1x6 repeated ANOVA, metabolic measures were analysed using a 1x7 repeated measures ANOVA, and MBF was analysed using a two-way t-test.

 

Results:

The KE drink was generally well tolerated. One subject vomited both before and after ingesting the KE, thus their results are not included in this analysis. From baseline to final blood draw, BHB increased to over 2 mM (p < 0.001) (Figure 1A) and glucose decreased 20 mg/dL(p < 0.001). Left ventricular ejection fraction (+15%, p < 0.001), heart rate (+21%, p < 0.001), stroke volume (+12%, p = 0.002), and cardiac output (+35%, p < .001) (Figure 1B) all increased during the two hour period post KE consumption (Table 2). End-systolic volume decreased (-19%; p < 0.001) and end-diastolic volume did not change (-3%; p = 0.15) (Table 2). MBF increased by 24% (p < 0.001) (Figure 1C).

Conclusion:

A ready to drink KE beverage increases cardiac output and MBF in a time and [BHB] dependent manner over the course of two hours in healthy adults. Future work is warranted to investigate potential benefits in patients with compromised cardiac function.