Acute Echocardiographic Effects of Exogenous Ketone Administration in Healthy Participants

Selvaraj, Senthil; Hu, Robert W.; Vidula, Mahesh K.; Dugyala, Supritha; Tierney, Ann; Ky, Bonnie; Margulies, Kenneth B.; Shah, Svati H.; Kelly, Daniel P.; Bravo, Paco E.

doi:10.1016/j.echo.2021.10.017

Cited by 32 publications

(21 citation statements)

References 29 publications

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“…We did not observe an increase in LVEF, which might be explained by our study participants having a normal baseline LVEF (57% ± 8). In patients with heart failure, intravenous ketone esters increase cardiac output in a dose-dependent manner (21), and in a study on healthy participants, a single oral dose of ketone esters reaching higher BHB levels than in the present study [median blood-BHB concentration: 3.23 mmol/L (IQR: 2.40-4.97)] LVEF was increased by 3.1%, GLS by 2.0%, and right ventricle S' by 1.1 cm (25). Myocardial BHB utilization is furthermore increased in proportion to blood ketone levels (26), indicating that our failure to report an increase in LVEF and cardiac output could also be dose dependent.…”

Section: Improvement In Cardiac Function Following Treatment With Ora...supporting

confidence: 48%

Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study

Wodschow

Davidovski²,

Christensen³

et al. 2023

Front. Nutr.

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BackgroundCOVID-19 is associated with subclinical myocardial injury. Exogenous ketone esters acutely improve left myocardial function in healthy participants and patients with heart failure, but the effects have not been investigated in participants previously hospitalized for COVID-19.MethodsThis is a randomized placebo-controlled double-blind crossover study comparing a single oral ketone ester dose of 395 mg/kg with placebo. Fasting participants were randomized to either placebo in the morning and oral ketone ester in the afternoon or vice versa. Echocardiography was performed immediately after intake of the corresponding treatment. Primary outcome was left ventricular ejection fraction (LVEF). Secondary outcomes were absolute global longitudinal strain (GLS), cardiac output and blood oxygen saturation. Linear mixed effects models were used to assess differences.ResultsWe included 12 participants previously hospitalized for COVID-19 with a mean (±SD) age of 60 ± 10 years. The mean time from hospitalization was 18 ± 5 months. Oral ketone esters did not increase LVEF between placebo and oral ketone ester [mean difference: −0.7% (95% CI −4.0 to 2.6%), p = 0.66], but increased GLS [1.9% (95% CI: 0.1 to 3.6%), p = 0.04] and cardiac output [1.2 L/min (95% CI: −0.1 to 2.4 L/min), p = 0.07], although non-significant. The differences in GLS remained significant after adjustment for change in heart rate (p = 0.01). There was no difference in blood oxygen saturation. Oral ketone esters increased blood ketones over time (peak level 3.1 ± 4.9 mmol/L, p < 0.01). Ketone esters increased blood insulin, c-peptide, and creatinine, and decreased glucose and FFA (all p ≤ 0.01) but did not affect glucagon, pro-BNP, or troponin I levels (all p > 0.05).ConclusionIn patients previously hospitalized with COVID-19, a single oral dose of ketone ester had no effect on LVEF, cardiac output or blood oxygen saturation, but increased GLS acutely.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT04377035.

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Section: Improvement In Cardiac Function Following Treatment With Ora...supporting

confidence: 48%

Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study

Wodschow

Davidovski²,

Christensen³

et al. 2023

Front. Nutr.

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show abstract

“…Ketone bodies have been reported to exert beneficial actions in rodents and humans with heart failure [ 4 , 7 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. On the other hand, ketones can induce myocellular insulin resistance [ 17 , 18 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…Dietary supplementation of ketone bodies has been shown to have multiple beneficial effects on both health and disease. For example, ketone bodies serve as an alternative fuel in trained athletes [ 8 ] and were reported to be beneficial in animal models and patients with heart failure [ 4 , 10 , 11 , 12 , 13 ]. Additionally, ketone body infusion specifically improved cognitive parameters in patients with type 2 diabetes [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Ketone Body Exposure of Cardiomyocytes Impairs Insulin Sensitivity and Contractile Function through Vacuolar-Type H+-ATPase Disassembly—Rescue by Specific Amino Acid Supplementation

Wang

Neumann

Westenbrink

et al. 2022

IJMS

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The heart is metabolically flexible. Under physiological conditions, it mainly uses lipids and glucose as energy substrates. In uncontrolled diabetes, the heart switches towards predominant lipid utilization, which over time is detrimental to cardiac function. Additionally, diabetes is accompanied by high plasma ketone levels and increased utilization of energy provision. The administration of exogenous ketones is currently being investigated for the treatment of cardiovascular disease. Yet, it remains unclear whether increased cardiac ketone utilization is beneficial or detrimental to cardiac functioning. The mechanism of lipid-induced cardiac dysfunction includes disassembly of the endosomal proton pump (named vacuolar-type H+-ATPase; v-ATPase) as the main early onset event, followed by endosomal de-acidification/dysfunction. The de-acidified endosomes can no longer serve as a storage compartment for lipid transporter CD36, which then translocates to the sarcolemma to induce lipid accumulation, insulin resistance, and contractile dysfunction. Lipid-induced v-ATPase disassembly is counteracted by the supply of specific amino acids. Here, we tested the effect of ketone bodies on v-ATPase assembly status and regulation of lipid uptake in rodent/human cardiomyocytes. 3-β-hydroxybutyrate (3HB) exposure induced v-ATPase disassembly and the entire cascade of events leading to contractile dysfunction and insulin resistance, similar to conditions of lipid oversupply. Acetoacetate addition did not induce v-ATPase dysfunction. The negative effects of 3HB could be prevented by addition of specific amino acids. Hence, in sedentary/prediabetic subjects ketone bodies should be used with caution because of possible aggravation of cardiac insulin resistance and further loss of cardiac function. When these latter maladaptive conditions would occur, specific amino acids could potentially be a treatment option.

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“…BHB infusion has been shown to specifically improve working memory performance in patients with T2DM in the absence of changes in global cognition ( 41 ). Even in healthy people, exogenous administration of ketones has been shown to improve the cardiac function ( 42 ). In addition, data from animal experiments have shown that ketones aid the prevention and treatment of heart failure by reducing inflammation ( 43 ), normalizing myocardial adenosine triphosphate production ( 44 ), and ameliorating pathologic cardiac remodeling and dysfunction ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

Association of Serum β-Hydroxybutyrate and Coronary Artery Disease in an Urban Chinese Population

Yang

Wang

et al. 2022

Front. Nutr.

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Ketone bodies, including β-hydroxybutyrate (BHB), acetoacetate (AA), and acetone, can substitute and alternate with glucose under conditions of fuel/food deficiency. Ketone-body metabolism is increased in a myriad of tissue-metabolism disorders. Perturbations in metabolism are major contributors to coronary artery disease (CAD). We investigated the association of BHB with CAD. A total of 2,970 people of Chinese Han ethnicity were enrolled. The Gensini score was calculated for all patients who had positive findings. The serum level of BHB and other laboratory parameters were measured. The association of serum levels of metabolites with traditionally risk factors and CAD severity was analyzed. The BHB was found to be associated with some traditional risk factors of CAD and CAD severity, as determined by the Gensini score or the number of diseased regions. Moreover, BHB was associated with the T3/T1 tertiles of the Gensini score after the adjustment for traditional risk factors by multivariable logistic regression analysis. The association of BHB with CAD severity was more obvious in women. Taken together, these data suggest that the circulating BHB level is independently associated with CAD severity, and that this association is more pronounced in women.

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Acute Echocardiographic Effects of Exogenous Ketone Administration in Healthy Participants

Cited by 32 publications

References 29 publications

Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study

Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study

Ketone Body Exposure of Cardiomyocytes Impairs Insulin Sensitivity and Contractile Function through Vacuolar-Type H+-ATPase Disassembly—Rescue by Specific Amino Acid Supplementation

Association of Serum β-Hydroxybutyrate and Coronary Artery Disease in an Urban Chinese Population

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