Absorption, Anti-inflammatory, Antioxidant, and Cardioprotective Impacts of a Novel Fasting Mimetic Containing Spermidine, Nicotinamide, Palmitoylethanolamide, and Oleoylethanolamide: A Pilot Dose-Escalation Study in Healthy Young Adult Men

Abstract

This pilot dose-escalation study evaluated the absorption and metabolism of a novel fasting mimetic formulation containing spermidine, nicotinamide, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) taken as oral supplements in young adults. Five healthy men consumed a standardized breakfast, followed by control (wheat flour) or low, medium, or high doses of supplements containing spermidine, nicotinamide, PEA, and OEA 2 h later. Blood was drawn at 0, 1, 2, and 4 h after the supplement (2, 3, 4, and 6 h postprandial). Plasma concentrations of spermidine, 1-methylnicotinamide (1-MNA), PEA and OEA were quantified by LC-MS. The secretion of tumor necrosis factor alpha (TNF-α) and production of reactive oxygen species (ROS) by stimulated macrophages incubated with plasma, and cholesterol efflux capacity (CEC) of plasma were analyzed. Plasma 1-MNA, PEA and OEA concentrations increased after supplement intake (P < 0.05). Spermidine concentrations decreased in the control arm (P < 0.05) but not the supplement arms. Net incremental area under the curve for TNF-α and ROS in stimulated macrophages decreased when incubated with plasma following supplement intake (P < 0.05). Intake of the combined supplements showed they were bioavailable and increased in plasma in a dose-dependent manner, and provide preliminary data showing enhanced plasma anti-inflammatory and antioxidant functions.This trial was registered at clinicaltrials.gov (NCT05017428).