Improved cardiac function by medium-chain triacylglycerol intake links to increased fat and ketone body availability

Abstract Background Cardiac fat oxidation is impaired in heart failure with reduced ejection fraction (HFrEF). This appears linked to impaired mitochondrial uptake of long-chain fatty acids, resulting in increased reliance on ketone bodies. Increased ketone body availability improves cardiac function in HFrEF but problematically may also lower blood pH. Intake of medium-chain triacylglycerol (MCT) extracted from coconut oil induces both ketogenesis and whole-body fat oxidation - but may in theory increase lipid and cholesterol levels. Purpose The purposes were to study the effects of acute MCT intake on 1) cardiac function in individuals with HFrEF and matched controls, and 2) the potential caveats of lowered blood pH and increased circulating lipid and cholesterol levels in healthy individuals. We hypothesized that intake of MCT would increase ketone body availability and have beneficial effect on cardiac function, and explore the effect on blood pH and circulating lipid levels. Methods Study 1: Ten patients with HFrEF on stable heart failure medication (NYHA II-III, left ventricular ejection fraction (LVEF) 42±8% (mean±SD), age 60±9yrs, body mass index (BMI) 26.1±3.2 kg/m2) and thirteen matched healthy individuals (LVEF 63±5%, age 64±16yrs, BMI 24.3±3.3 kg/m2) ingested 0.5g/kg MCT or long-chain triacylglycerol (LCT) in a randomized cross-over trial assessing blood ketone body levels and cardiac function with magnetic resonance imaging. Study 2: sixteen healthy men (age 31±7 years, BMI 27.5±5.4 kg/m²) participated in a randomized cross-over trial with a one-week intervention and a 14-day washout. They ingested 20-60 g of MCT or LCT daily to assess acute and longer-term effects on blood pH, and circulating lipids and cholesterol levels. Results MCT intake increased blood ketone body levels by ~1mmol/l (p0.05). Study 1: In patients with HFrEF, MCT increased cardiac output (CO) by 16±5% (mean±SE, p0.05), LVEF by 5±2%-points (43±3 vs. 48±3%, p0.001), and cardiac power output (CPO) by 14±5% (p0.05) relative to LCT. In healthy individuals, MCT increased CO by 10±4% (p0.01), LVEF by 3±1%-points (61±1 vs. 64±2%, p0.01), and CPO by 9±4% (p0.05) relative to LCT. Relative to LCT, MCT lowered systemic vascular resistance by 17±2% (p0.001) in patients with HFrEF and 14±3% in healthy individuals. Study 2: Acute MCT intake did not affect blood pH, and prevented a postprandial rise in circulating triacylglycerol levels. One week MCT intake did not affect circulating triacylglycerol or cholesterol levels. Conclusion Medium-chain triacylglycerol intake improves cardiac output and cardiac function, likely via a combination of increased ketone body availability, and lower vascular resistance, without affecting pH, lipids, or cholesterol. Unlike ketone body treatment, it is more feasible due to better tolerability, absence of blood acidification, and lower cost, warranting further research into its potential for heart failure treatment.Relative changes in cardiac function