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. 2025 Jul 7;137(2):350-353.
doi: 10.1161/CIRCRESAHA.125.326414. Epub 2025 May 28.

Cardiac Ketone Body Oxidation Enhances Exercise Performance

Kara R Gouwens  1   2 , Ernesto Pena Calderin  1 , Jada Okhiria  1   2 , Daniel C Nguyen  1   2 , Emily B Schulman-Geltzer  1 , Yania Martinez-Ondaro  1 , Maleesha De Silva  1 , Helen E Collins  1 , Yibing Nong  1 , Sophia M Sears  1 , Matthew A Nystoriak  3 , Bradford G Hill  1
Affiliations

Cardiac Ketone Body Oxidation Enhances Exercise Performance

Kara R Gouwens et al. Circ Res. .

Erratum in

  • Correction to: Cardiac Ketone Body Oxidation Enhances Exercise Performance.
    Gouwens KR, Pena Calderin E, Okhiria J, Nguyen DC, Schulman-Geltzer EB, Martinez-Ondaro Y, De Silva M, Collins HE, Nong Y, Sears SM, Nystoriak MA, Hill BG. Gouwens KR, et al. Circ Res. 2025 Sep 26;137(8):e176. doi: 10.1161/RES.0000000000000732. Epub 2025 Sep 25. Circ Res. 2025. PMID: 40997156 No abstract available.
No abstract available

Keywords: aging; dietary supplements; exercise tolerance; heart failure; metabolism; myocytes, cardiac; vasodilation.

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Conflict of interest statement

Data supporting the conclusions of this study are included in the article and accompanying statistical table. Analytic methods are available upon request. The authors declare no conflicts of interest. Artificial intelligence was not used in this work.

Figures

Figure.
Figure.
Cardiomyocyte ketone body catabolism underlies 3-hydroxybutyrate (3-OHB)–induced improvement in acute exercise capacity. A, Schematic of exercise capacity test (ECT) protocol: male αMHC-MerCreMer (hemizygous)×Bdh1 (3-hydroxybutyrate dehydrogenase 1)fl/fl mice and their Cre− Bdh1fl/fl littermates (6–8 months of age at the beginning of the protocol; C57BL/6J background) were subjected to ECTs before (baseline) and after tamoxifen administration (post-TAM), followed by groups receiving ≈100-µL oral gavage of vehicle (water) or 50% ketone monoester (KME) ≈40 min before the final ECT. Gray bars in the schematic indicate independent acclimation treadmill sessions before ECTs. Personnel performing ECTs were blinded to genotype and group. B, i., Total (left) and relative (right) distance and (ii.) total (left) and relative work (right) at baseline and post-TAM of csBDH1−/− mice compared with controls (Wilcoxon matched-pairs signed rank for total distance and work; Mann-Whitney U test for relative distance and work; n=14/group). iii., Circulating lactate (left) and 3-OHB (right) levels at rest and fatigue in control vs csBDH1−/− mice at baseline and post-TAM (2-way repeated measures ANOVA, n=14/group). iv., Cardiac work (left ventricular [LV] pressure×heart rate) before and after norepinephrine-mediated cardiac stress tests in control and csBDH1−/− mice (2-way repeated measures ANOVA, post hoc: Fischer Least Significant Difference test, n=7/group). C, i., Electrospray ionization mass spectrum of KME in positive mode; * signifies fragments of [M+H+], and # signifies charged clusters or impurities. ii., Circulating 3-OHB levels over 150 min following oral gavage of 0%, 20%, or 50% KME:water in male, wild-type C57BL/6J mice (age, 23 weeks); P value shown represents comparisons between water (−) vs 20% and 50% KME:water at t60 (mixed effects analysis, n=2–3/group). D, Distance (i.) and work (ii.) from mice that received oral gavage of water or KME (Kruskal-Wallis, post hoc: Dunn multiple comparison, n=7/group). iii., Circulating lactate (top) and 3-OHB levels (bottom)±KME at rest and fatigue in control and csBDH1−/− mice (mixed effects analysis, n=7). For all statistical comparisons, P>0.05 was considered NS; post hoc test: Šídák multiple comparisons test was used unless stated otherwise.
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