Ketogenic diets have shown promise in treating diabetes and metabolic syndrome, with established use in athletes, though their effectiveness in heart disease and dementia remains less understood. Research, often in mice or short-term human trials, has generated promising data. The National Institutes of Health recently awarded a $3.5 million grant for a long-term, double-blind clinical trial to investigate the effects of ketone ester supplementation on frailty, based on ketone bodies’ interaction with aging biology. This trial, named TAKEOFF, involves researchers from the Ohio State University, the University of Connecticut, and the Buck Institute for Research on Aging. The study aims to explore the potential applications of ketone bodies in addressing aging-related conditions, including issues like glucose metabolism decline and insulin resistance.