Palmitoylethanolamide: A Natural Compound for Health Management

Abstract

All nations which have undergone a nutrition transition have experienced increased frequency and falling latency of chronic degenerative diseases, which are largely driven by chronic inflammatory stress. Dietary supplementation is a valid strategy to reduce the risk and severity of such disorders. Palmitoylethanolamide (PEA) is an endocannabinoid-like lipid mediator with extensively documented anti-inflammatory, analgesic, antimicrobial, immunomodulatory and neuroprotective effects. It is well tolerated and devoid of side effects in animals and humans. PEA’s actions on multiple molecular targets while modulating multiple inflammatory mediators provide therapeutic benefits in many applications, including immunity, brain health, allergy, pain modulation, joint health, sleep and recovery. PEA’s poor oral bioavailability, a major obstacle in early research, has been overcome by advanced delivery systems now licensed as food supplements. This review summarizes the functionality of PEA, supporting its use as an important dietary supplement for lifestyle management.

(Wh)olistic (E)ndocannabinoidome-Microbiome-Axis Modulation through (N)utrition (WHEN) to Curb Obesity and Related Disorders

“…Indeed, a well-balanced dietary approach would be a key to keep a check on DNL. In addition, to derive the maximum benefits from PEA, the consumption of micronized PEA may work as an effective supplement [ 55 ]. Indeed, PEA has been suggested to play several beneficial actions in metabolic flexibility, obesity, chronic pain, and neurodegenerative, central, and peripheral inflammatory disorders through its various mechanisms of actions, including, i) synergy with eCBs in their activation of cannabinoid receptors and activation/desensitization of TRPV1 channels ("entourage effect") [ 56 ]; ii) stimulatory action on 2-AG levels via DAGL activation [ 57 ]; iii) direct activation of either PPAR-α [ 58 ] or GPR55 [ 24 , 59 ]; iv) triggering the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) [ 49 ].…”

“…PEA is a naturally occurring lipid ingredient contained in foods [ 129 ]. A plethora of evidence suggests that PEA is an anti-inflammatory, analgesic, and neuroprotective mediator acting on several molecular targets in central and peripheral organs and systems [ 55 , 102 ]. Bachur and colleagues [ 130 ] were the first to report the presence of PEA in mammalian tissues.…”

“…So far, only a few studies have addressed the association between the intake or levels of specific fatty acids with patterns of endogenous fatty acid amides in humans, particularly with C16:0 and its ethanolamide, PEA. However, numerous trials have been conducted demonstrating the safety and efficacy of PEA supplementation [ 55 , 131 ]. PEA is released in the human body 'on-demand;' therefore, providing a secure niche by maintaining C16:0 tissue levels is crucial.…”

“…The beneficial effects of PEA and OEA on the gut microbiome have been recently explored [ 55 , 74 , 212 – 216 ], and henceforth, the compound has become popular among microbiologists. Recently, Guida et al [ 214 ] demonstrated that PEA (10 mg.kg –1 , i.p.)…”

Mutual Links between the Endocannabinoidome and the Gut Microbiome, with Special Reference to Companion Animals: A Nutritional Viewpoint

“…Summarizing, AEA-like bacterial lipopolysaccharides and inflammatory cytokines-is considered a "gate opener" with regard to gut barrier function, while PEA exerts a beneficial effect on the permeability barrier and is considered a "gate keeper" [140,159].…”