Palmitoylethanolamide, an endogenous fatty acid amide, and its pleiotropic health benefits: A narrative review

The global nutritional transition has led to the increased frequency and severity of chronic degenerative diseases worldwide, primarily driven by chronic inflammatory stress. At mealtimes, various pharmaceutical products aim to prevent such inflammatory stress, but they usually cause various systemic side effects. Therefore, the supplementation of natural and safe ingredients is a promising strategy to reduce the risk and severity of inflammatory stress-related diseases. Palmitoylethanolamide (PEA), an endocannabinoid-like mediator, has been extensively studied for its diverse actions, including anti-inflammatory, antimicrobial, immunostimulatory, neuroprotective, and pain-reducing effects, with high tolerability and safety in both animals and humans. Because of its multiple molecular targets and mechanisms of action, PEA has demonstrated therapeutic benefits in various diseases, including neurological, psychiatric, ophthalmic, metabolic, oncological, renal, hepatic, immunological, rheumatological, and gastrointestinal conditions. The current review highlights the roles and functions of PEA in various physiological and pathological conditions, further supporting its use as an important dietary agent.