1. Introduction
inflammation, allergy, Allergic rhinitis, rhinitis, nasal congestion, hypersensitivities, autism
DISORDER, INFLAMMATION, ALLERGIC RHINITIS, ALLERGY, PATHOPHYSIOLOGY, RHINITIS, HYPERSENSITIVITIES, PATHOLOGY, INFLAMMATORY RESPONSE
Background: Allergic rhinitis (AR) is an inflammatory, symptomatic disorder stimulated by antigen-specific immunoglobulin E inflammation in response to allergens. Current treatments include the use of corticosteroids and antihistamines to reduce inflammation by preventing histamine release. Palmitoylethanolamide (PEA) is reported to be an alternative treatment, shown to downregulate mast cell activation and increase the synthesis of endocannabinoid 2-Arachidonoylglycerol to reduce histamine and the symptoms of AR. Method: A double-blind, randomised, placebo-controlled clinical trial in which 108 participants presenting with seasonal AR were supplemented with either 350 mg of PEA (Levagen+) or a placebo daily for two weeks. Symptom scores were recorded using the reflective total nasal symptom score (rTNSS) twice a day (morning and evening) for the two weeks, and blood was taken at baseline and week 2. Results: 101 participants completed the study with no baseline group differences. No significant difference was seen between groups for allergy symptoms scores (rTNSS) throughout the 14 days of treatment. A sub-group analysis of participants scoring over four (mild-to-moderate) on the total rTNSS at baseline showed that Levagen+ significantly reduced scores compared to the placebo group. Only 36 participants had full sets of blood taken due to COVID-19. The pathology results showed a significant difference in change from baseline between groups. The Levagen+ group had a significant decrease from baseline in histamine, IL-4, IL-8, IL-10, and TNF-α. The placebo group only had a reduction in IL-4. Conclusion: The results of this study show that Levagen+ can alleviate AR symptoms, resulting in a reduction in histamine and inflammatory markers.Allergic rhinitis (AR) is an inflammatory, symptomatic disorder triggered by antigen-specific immunoglobulin E (IgE) inflammation in response to allergen exposure in the nasal mucosa [Allergic rhinitis exhibits a complex pathophysiology that encompasses various molecular mechanisms and the involvement of inflammatory and immune cells. Both acute and chronic reactions in AR are orchestrated by the binding of allergens, such as pollen or mites, to IgE receptors situated on mast cells and basophils [Among the pro-inflammatory mediators, histamine assumes a central role in AR, primarily responsible for activating sensory nerve endings in nasal nociceptors and prompting the release of acetylcholine from nasal parasympathetic nerves. This acetylcholine release, in turn, leads to increased mucus secretion, contributing to nasal congestion and a runny nose [Following exposure to an allergen, histamine is one of the main contributors to initiating an immune response [The intricate nature of AR pathophysiology has presented challenges in its treatment, leading to the development of various therapeutic options, including the emergence of alternative natural treatments aimed at addressing and preventing AR symptoms. As hypersensitivities become more prevalent, conventional treatments like antihistamines primarily focus on inhibiting the binding of histamine released from mast cells to histamine receptors to help prevent the inflammatory response triggered by IgE mast cell activation [PEA has been reported to downregulate mast cell activation and inhibit the release of mast cell mediators, including histamine [However, both endogenous levels of PEA and exogenous PEA administration have previously been reported to be insufficient to mitigate a significant inflammatory response due to poor absorption, resulting in a low plasma concentration [To the best of our knowledge, there have been no clinical studies to date that specifically investigate the impact of PEA on allergy symptoms, such as AR. One study by Antonucci (2015) supplemented a child with autism and allergy symptoms, including rhinitis, with 600 mg of PEA daily for one month and was able to show improvements in allergy symptoms, although there were no differences in IgE levels [Therefore, building on prior research and recognizing the potential of PEA as a therapeutic choice for individuals with AR, the aim of the present study was to assess the impact of a PEA supplement enriched with dispersion technology to aid absorption (Levagen+) in alleviating allergy symptoms in comparison to a placebo group during a 14-day treatment period. Our hypothesis is that the administration of Levagen+ will result in a reduction in the severity of allergy symptoms when compared to a placebo over the course of a 2-week intervention period.