Palmitoylethanolamide (PEA) belongs to the N-acyl ethanolamines (NAEs), a group of endogenous compounds
involved in a variety of physiological processes, including energy homeostasis and inflammation. This review focuses on
the analysis of PEA in plasma and tissues and discusses effects of diet and some pathological processes on PEA levels.
Originally isolated from egg yolk, PEA has been detected in a variety of tissues and plasma of different species. The
compound is present at relatively high levels compared to other NAEs and now mostly analysed using liquid
chromatography coupled to mass spectrometry. PEA plasma concentrations show marked fluctuations during the day.
However, concentrations in tissues are likely to be more relevant than those in plasma. Most studies suggest that
compared to other NAEs, tissue PEA tissue levels are not influenced by changes in dietary fatty acid composition. Effects
of inflammation and disease on PEA tissue levels show differences between different models and studies. Therefore, more
research is needed on the endogenous role and tissue kinetics of PEA during disease. The rediscovery of the therapeutic
potential of PEA has fuelled research and the development of new pharmaceutical formulations. With regard to this there
is a need for better kinetic data and models, preferably also on its tissue disposition. Moreover, it is important to learn
more about effects of exogenous PEA on the kinetics of other NAEs (and endocannabinoids) and effects of inhibiting its
breakdown using inhibitors of the degrading enzymes fatty acid amide hydrolase or N-acylethanolamine-hydrolyzing acid
Keywords: Inflammation, liquid chromatography-mass spectrometry, palmitoylethanolamide, kinetics, endocannabinoids
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