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Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study
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: T...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9947401/ https://www.ncbi.nlm.nih.gov/pubmed/36845050 http://dx.doi.org/10.3389/fnut.2023.1131192 |
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author | Wodschow, Helena Zander Davidovski, Filip Søskov Christensen, Jacob Lassen, Mats Christian Højbjerg Skaarup, Kristoffer Grundtvig Nygaard, Hanne Møller, Niels Rungby, Jørgen Biering-Sørensen, Tor Rossing, Peter Jensen, Nicole Jacqueline Laursen, Jens Christian |
author_facet | Wodschow, Helena Zander Davidovski, Filip Søskov Christensen, Jacob Lassen, Mats Christian Højbjerg Skaarup, Kristoffer Grundtvig Nygaard, Hanne Møller, Niels Rungby, Jørgen Biering-Sørensen, Tor Rossing, Peter Jensen, Nicole Jacqueline Laursen, Jens Christian |
author_sort | Wodschow, Helena Zander |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9947401 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99474012023-02-24 Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study Wodschow, Helena Zander Davidovski, Filip Søskov Christensen, Jacob Lassen, Mats Christian Højbjerg Skaarup, Kristoffer Grundtvig Nygaard, Hanne Møller, Niels Rungby, Jørgen Biering-Sørensen, Tor Rossing, Peter Jensen, Nicole Jacqueline Laursen, Jens Christian Front Nutr Nutrition 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. Frontiers Media S.A. 2023-02-09 /pmc/articles/PMC9947401/ /pubmed/36845050 http://dx.doi.org/10.3389/fnut.2023.1131192 Text en Copyright © 2023 Wodschow, Davidovski, Christensen, Lassen, Skaarup, Nygaard, Møller, Rungby, Biering-Sørensen, Rossing, Jensen and Laursen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Nutrition Wodschow, Helena Zander Davidovski, Filip Søskov Christensen, Jacob Lassen, Mats Christian Højbjerg Skaarup, Kristoffer Grundtvig Nygaard, Hanne Møller, Niels Rungby, Jørgen Biering-Sørensen, Tor Rossing, Peter Jensen, Nicole Jacqueline Laursen, Jens Christian Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study |
title | Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study |
title_full | Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study |
title_fullStr | Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study |
title_full_unstemmed | Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study |
title_short | Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study |
title_sort | oral ketone esters acutely improve myocardial contractility in post-hospitalized covid-19 patients: a randomized placebo-controlled double-blind crossover study |
topic | Nutrition |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9947401/ https://www.ncbi.nlm.nih.gov/pubmed/36845050 http://dx.doi.org/10.3389/fnut.2023.1131192 |
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