Three-week alternate day fasting improves myocardial flow reserve and reduces oxygen use in individuals with overweight

Context Alternate day fasting (ADF) is a dietary regimen with prolonged fasting periods associated with metabolic and cardiovascular benefits. It remains unclear if ADF improves cardiac function and metabolism to explain these benefits. Objective This study aimed to investigate the effects of a three-week ADF intervention on myocardial efficiency, perfusion, and substrate metabolism in overweight/obese individuals. Methods Sixteen participants with overweight (BMI: 32±1.9 kg/m2) completed this randomized crossover study comparing ADF with a standard diet. Dynamic cardiac positron emission tomography scans were performed using five tracers: [15O]water to assess myocardial blood flow and flow reserve (MFR), [11C]acetate to measure myocardial oxygen consumption (MVO2) and myocardial external efficiency (MEE), and [11C]β-hydroxybutyrate ([11C]OHB), [11C]palmitate and [18F]fluorodeoxyglucose to assess metabolism of OHB, free fatty acid (FFA), and glucose, respectively. Blood samples were analyzed for OHB, FFA, glucose, lactate, and insulin. Blood pressure, heart rate, cardiac output, and left ventricular mass, ejection fraction and volumes were assessed. Results ADF increased circulating ketones on fasting days (peak: 0.67±0.09 mmol/L), which remained elevated on eating days (0.20±0.03 mmol/L). However, myocardial substrate metabolism remained unaltered following ADF. Blood pressure and cardiac output significantly decreased after ADF (systolic/diastolic: 13/9 mmHg and 0.5 L/min, respectively; p<0.001). MVO2 decreased by 10% (p=0.01), and total left ventricular energy use by 19% (p<0.01). Resting myocardial perfusion decreased by 9% (p<0.05), and MFR increased by 34% (p<0.01). Conclusions A three-week ADF regimen reduced blood pressure and MVO2, and improved MFR, suggesting ADF may provide a non-pharmacological strategy to improve cardiovascular health in individuals with overweight.