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

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 hours later. Blood was drawn at 0, 1, 2, and 4 hours after the supplement (2, 3, 4, and 6 hours postprandial). Plasma concentrations of spermidine, 1-methylnicotinamide, PEA and OEA were quantified by liquid chromatography-mass spectrometry. The secretion of tumor necrosis factor alpha and production of reactive oxygen species by stimulated macrophages incubated with plasma, and cholesterol efflux capacity of plasma were analyzed. Plasma 1-methylnicotinamide, PEA, and OEA concentrations increased after supplement intake (P < .05). Spermidine concentrations decreased in the control arm (P < .05) but not the supplement arms. Net incremental area under the curve for tumor necrosis factor alpha and reactive oxygen species in stimulated macrophages decreased when incubated with plasma following supplement intake (P < .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).