Doctor of Philosophy, The Ohio State University, 2024, Kinesiology

Introduction: Various methods of achieving beneficial levels of ketones have been theorized to serve as a potential therapeutic for patients suffering from heart failure. Ketone uptake by the heart is rapid and may serve as an efficient alternative fuel that bypasses myocardial metabolic dysfunction. Ketones may also work through other pleiotropic mechanisms (e.g., hemodynamic, cell signaling) to impact cardiac performance. To further elucidate the influence of ketones on cardiovascular responses, two exploratory studies were performed here in separate cohorts of healthy adults to investigate the effects of 50g ketone ester (KE) ingestion on resting and exercise-induced metabolic and cardiovascular responses. Methods: 1) Study 1: This was a single visit acute imaging and supplementation study (n = 20). Subjects reported to the MRI facility following an overnight fast and underwent baseline cardiovascular imaging including quantitative myocardial perfusion. Subjects then consumed the test article, ketone ester (KE) or placebo (PL) and underwent repeated cardiac imaging every 15-30min. Two hours following consumption, subjects underwent a final imaging scan and received a final quantitative perfusion acquisition. Ketones and glucose were measured at baseline and every imaging timepoint. 2) Study 2: A cohort of recreationally active adults (n = 12) were enrolled to complete a double blind, balanced, crossover study to examine the effects of KE ingestion compared to a calorically-matched fat-based placebo on measures of maximal oxygen consumption (VO2max) and running efficiency. Subjects presented to the testing facility fasted then underwent baseline fingersticks and drank the supplement immediately after. Metabolic and cardiovascular measures were collected every 15-30min following supplementation. Two hours following ingestion, the subject began the Bruce Protocol maximal exercise test. Results: 1) Study 1: Following KE consumption venous beta-hydroxybutyrate (BH (open full item for complete abstract)

Committee: Jeff Volek (Advisor); Orlando Simonetti (Committee Member); Yuchi Han (Committee Member); Brian Focht (Committee Member) Subjects: Kinesiology; Physiology