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

Front Nutr. 2023 Feb 9;10:1131192. doi: 10.3389/fnut.2023.1131192. eCollection 2023.


Background: COVID-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.

Methods: This 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.

Results: We 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).

Conclusion: In 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 registration: https://clinicaltrials.gov/, identifier NCT04377035.

Keywords: ketone bodies; myocardial contractility; myocardial metabolism; post COVID-19; subclinical myocardial injury.

Associated data

  • ClinicalTrials.gov/NCT04377035

Grant support

Funding for the study was provided by the Becket-Foundation Grant for Medical Research and the Carl and Ellen Hertz Foundation Grant for Medical- and Natural Science. Ketone ester and taste-matching placebo for the study were donated by the company KetoneAid by initiative of the research group.