Comparison of Exogenous Ketone Administration versus Dietary Carbohydrate Restriction on Myocardial Glucose Suppression: A Crossover Clinical Trial

Abstract

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Metabolomic Signatures of Myocardial Glucose Uptake on Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography

“…The mean age was 30 ± 7 years, 50% were female, 45% were non-White, and the mean fasting time before FDG injection was 16.0 ± 0.9 hours. 2 MGS failure occurred in 11 of 20 scans with the KE and 8 of 37 with the KD. Figure 1A depicts volcano plots for the relationship between 61 metabolites and MGU for the 2 KD visits (combined) and the KE visit.…”

“…However, to highlight pathologic myocardial glucose uptake (MGU), physiological MGU must be suppressed, often accomplished through a ketogenic diet (KD). 1 Failure to suppress physiological MGU occurs in ∼20% of subjects even following strict, highly supervised dietary interventions, 1 , 2 potentially leading to misdiagnosis, repeat scans, and unnecessary costs.…”

“…In a crossover trial (KEETO-CROSS [Ketogenic Endogenous versus Exogenous Therapies for Myocardial Glucose Suppression]; NCT04275453 ), we showed that ketone ester (KE) drink (exogenous ketosis) was inferior to the KD (endogenous ketosis) for suppressing MGU. 2 However, circulating ketone (beta-hydroxybutyrate [BHB]) levels strongly predicted myocardial glucose suppression (MGS) within each arm and could be used upstream of FDG-PET to assess myocardial preparation. Furthermore, the ketosis required to suppress the myocardium varied by technique (with significantly higher levels required for KE).…”

“…In KEETO-CROSS, participants free of cardiovascular disease (in whom any MGU could be assumed physiological) were randomly assigned to the KE (one visit) or KD (2 visits at 24 and 72 hours) arm, and crossed over after a >1-week washout period. 2 All 20 participants completed the KE arm, whereas 19 and 18 participants completed the 24- and 72-hour KD visits, respectively. The study was approved by an institutional review board, and informed consent was obtained.…”

“…At these 3 visits, FDG-PET was performed and MGU was analyzed according to a protocol previously described. 2 …”