Introduction
Periodic prolonged fasting (PF), defined here as ≥24 h of zero caloric intake, is one of the few known nutritional interventions capable of extending lifespan [Despite the well-characterized link between PF and immunomodulation, there remains a paucity of research dedicated to investigating the underlying molecular mediators of these effects, especially in humans. One mechanism underlying these immunomodulatory effects may be the avoidance of the well-known proinflammatory effects of the postprandial state, which, although varied in magnitude between individuals, have been shown to be largely universal [To address these knowledge gaps, we designed and performed a pilot clinical trial assessing 4 distinct nutritional states in each participant to determine the effects of 36 h of fasting on the plasma metabolome and macrophage functionalities of young healthy participants and discover potential molecular mediators of these effects.