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
Department of Endocrinology, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
Department of Cardiology, Copenhagen University Hospital, Gentofte Hospital, Copenhagen, Denmark.
Front Nutr. 2023 Feb 9;10:1131192. doi: 10.3389/fnut.2023.1131192. eCollection 2023.
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.
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.
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%), = 0.66], but increased GLS [1.9% (95% CI: 0.1 to 3.6%), = 0.04] and cardiac output [1.2 L/min (95% CI: -0.1 to 2.4 L/min), = 0.07], although non-significant. The differences in GLS remained significant after adjustment for change in heart rate ( = 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, < 0.01). Ketone esters increased blood insulin, c-peptide, and creatinine, and decreased glucose and FFA (all ≤ 0.01) but did not affect glucagon, pro-BNP, or troponin I levels (all > 0.05).
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.
https://clinicaltrials.gov/, identifier NCT04377035.
新型冠状病毒肺炎（COVID-19）与亚临床心肌损伤有关。外源性酮酯可急性改善健康参与者和心力衰竭患者的左心功能，但尚未在先前因COVID-19住院的参与者中研究其效果。
这是一项随机安慰剂对照双盲交叉研究，比较单次口服395mg/kg酮酯与安慰剂的效果。空腹参与者被随机分为上午服用安慰剂、下午服用口服酮酯，或反之。在摄入相应治疗后立即进行超声心动图检查。主要结局是左心室射血分数（LVEF）。次要结局是绝对整体纵向应变（GLS）、心输出量和血氧饱和度。使用线性混合效应模型评估差异。
我们纳入了12名先前因COVID-19住院的参与者，平均（±标准差）年龄为60±10岁。距住院的平均时间为18±5个月。口服酮酯在安慰剂和口服酮酯之间未增加LVEF[平均差异：-0.7%（95%CI -4.0至2.6%），P = 0.66]，但增加了GLS[1.9%（95%CI：0.1至3.6%），P = 0.04]和心输出量[1.2L/min（95%CI：-0.1至2.4L/min），P = 0.07]，尽管不显著。在调整心率变化后，GLS的差异仍然显著（P = 0.01）。血氧饱和度没有差异。口服酮酯随时间增加血酮水平（峰值水平3.1±4.9mmol/L，P < 0.01）。酮酯增加了血胰岛素、C肽和肌酐，并降低了血糖和游离脂肪酸（均P≤0.01），但不影响胰高血糖素、脑钠肽前体或肌钙蛋白I水平（均P>0.05）。
在先前因COVID-19住院的患者中，单次口服酮酯对LVEF、心输出量或血氧饱和度没有影响，但可急性增加GLS。
