Phytotherapics in COVID19: Why palmitoylethanolamide?

Abstract

At present, googling the search terms "COVID-19" and "Functional foods" yields nearly 500,000,000 hits, witnessing the growing interest of the scientific community and the general public in the role of nutrition and nutraceuticals during the COVID-19 pandemic. Many compounds have been proposed as phytotherapics in the prevention and/or treatment of COVID-19. The extensive interest of the general public and the enormous social media coverage on this topic urges the scientific community to address the question of whether which nutraceuticals can actually be employed in preventing and treating this newly described coronavirus-related disease. Recently, the Canadian biotech pharma company "FSD Pharma" received the green light from the Food and Drug Administration to design a proof-of-concept study evaluating the effects of ultramicronized palmitoylethanolamide (PEA) in COVID-19 patients. The story of PEA as a nutraceutical to prevent and treat infectious diseases dates back to the 1970s where the molecule was branded under the name Impulsin and was used for its immunomodulatory properties in influenza virus infection. The present paper aims at analyzing the potential of PEA as a nutraceutical and the previous evidence suggesting its anti-inflammatory and immunomodulatory properties in infectious and respiratory diseases and how these could translate to COVID-19 care.

A Combination of α-Lipoic Acid (ALA) and Palmitoylethanolamide (PEA) Blocks Endotoxin-Induced Oxidative Stress and Cytokine Storm: A Possible Intervention for COVID-19

“…In this scenario, PEA can explain its effects, which depend on its ability to act as a mast cell stabilizer (65). PEA has multitarget action related to several signaling pathways, which include TLR, nitric oxide, IL-6 and IL-1b by binding TLRs (66).…”

Management of Acute Lung Injury: Palmitoylethanolamide as a New Approach

“…Recent studies have proposed um-PEA as a potential adjunct in therapy for COVID patients, thanks to its ability to modulate inflammation and neuroinflammation, both peripherally and centrally [ 24 , 25 ]. Precisely these pleiotropic properties could be taken into consideration for the introduction of um-PEA in the COVID-19 multidrug regimen, thus avoiding an increase in the dosage of immunosuppressants by planning a synergistic therapy between um-PEA and the latter [ 26 , 27 ]. The mechanisms underlying ALI are still unclear, so in the present study, we used a model of intratracheally LPS-induced ALI to evaluate the effects of um-PEA 30 mg/kg on regulation of inflammatory process in acute lung disease.…”

Ultramicronized Palmitoylethanolamide Inhibits NLRP3 Inflammasome Expression and Pro-Inflammatory Response Activated by SARS-CoV-2 Spike Protein in Cultured Murine Alveolar Macrophages

“…The possibility to use PEA as a molecule able to prevent and treat infectious diseases dates to the 1970s where this autacoid local injury antagonist amide (ALIAmide) was branded under the name Impulsin and was used for its immunomodulatory properties in influenza virus infection [ 17 , 18 ] Nowadays, ultramicronized PEA (um-PEA), a new pharmaceutical form of PEA with higher efficacy and bioavailability compared to standard PEA [ 19 ], has been authorized in an ongoing clinical trial as an add-on therapy in the treatment of SARS-CoV-2. Although there are currently several trials on the possible use of PEA as a support to anti-COVID19 therapies [ 20 ] generically based on its anti-inflammatory activity, the molecular effects of PEA in the course of hyperinflammation processes induced by SARS-CoV-2 are yet to be characterized.…”