Palmitoylethanolamide (PEA) is a food component known since 1957. PEA is synthesized and metabolized in animal cells via a number of enzymes and exerts a multitude of physiological functions related to metabolic homeostasis. Research on PEA has been conducted for more than 50 years, and over 350 papers are referenced in PubMed describing the physiological properties of this endogenous modulator and its pharmacological and therapeutical profile. The major focus of PEA research, since the work of the Nobel laureate Levi-Montalcini in 1993, has been neuropathic pain states and mast cell related disorders. However, it is less known that 6 clinical trials in a total of nearly 4000 people were performed and published last century, specifically studying PEA as a therapy for influenza and the common cold. This was done before Levi-Montalcini’s clarification of PEA’s mechanism of action, analyzing the role of PEA as an anti-inflammatory agent. We will review in depth these studies, as the results support the effectiveness and safety of PEA in flu and respiratory infections. 1. Introduction Palmitoylethanolamide (PEA) is a food component known for more than 50 years. PEA is synthesized and metabolized by different animal cell types and also present in plants. It exerts a multitude of physiological functions related to metabolic and cellular homeostasis. PEA was already identified in the 50s of the last century as a therapeutic substance with potent anti-inflammatory properties. Since 1970, the anti-inflammatory and other immune-modulating properties of PEA have been shown in a number of placebo-controlled double-blind clinical trials on influenza and common cold. Positive results coincided with the clinical use of PEA in former Czechoslovakia under the brand name Impulsin. Since 2008, PEA has been marketed as a food for special medical purposes in Italy and Spain, under the brand name Normast (Epitech Srl). Recently, a food-supplement named PeaPure was introduced (JP Russell Science Ltd.). In the USA, PEA is under evaluation as a nutraceutical for inflammatory bowel syndrome (proposed brand name Recoclix, CM&D Pharma Ltd.; Nestlé). Research on PEA has been conducted since its discovery and over 350 papers are referenced in PubMed describing its physiological properties and role as endogenous modulator as well as its pharmacological and therapeutic effects. PEA is an interesting anti-inflammatory therapeutic substance and might also hold great promise for the treatment of a number of (auto)immune disorders, including inflammatory bowel disease and inflammatory
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