Palmitoylethanolamide for COVID-19

ABSTRACT Background Inflammation is at the core of many chronic conditions and exacerbates infectious conditions, including the severity of coronavirus disease 2019 (COVID-19) infections. Objectives This study aimed to examine the effects of a novel food supplement, palmitoylethanolamide (PEA), specifically Levagen+, as compared with a placebo on proinflammatory biomarkers in adults recently diagnosed with COVID-19 who were unvaccinated and nonhospitalized. Methods This study was a double-blind randomized placebo-controlled trial conducted October 2020–March 2021 (clinicaltrials.gov: NCT04912921). Participants aged 19–53 y were unvaccinated and recently infected with COVID-19 as indicated by a positive test result per RT-PCR or antigen test, and they reported to the test site following diagnosis as allowed by the CDC's return-to-work policy. Participants were stratified by age, sex, and BMI and randomly assigned by coin toss to receive 600 mg Levagen+ twice daily (LEV) or placebo tablets twice daily (CON) for 4 wk. At baseline and week 4, participants completed health histories, 24-h dietary recalls, anthropometrics, and nonfasting blood sampling. The primary outcomes were the 4-wk change between groups for IL-6, C-reactive protein, ferritin, intercellular adhesion molecule 1, soluble P-selectin (sP-selectin), and neutrophil/lymphocyte ratio. Multiple linear regression models were utilized to assess treatment effects on outcomes, adjusting for covariates. Results A total of 60 participants completed the study (LEV: n = 30; CON: n = 30). After 4 wk of supplementation, sP-selectin (β = −11.5; 95% CI: −19.8, −3.15; P = 0.0078), IL-1β (β = −22.9; 95% CI: −42.4, −3.40; P = 0.0222), and IL-2 (β = −1.73; 95% CI: −3.45, −0.065; P = 0.0492) concentrations were significantly reduced in the LEV group compared with the CON group. Conclusions Inflammatory mechanisms are crucial to optimal resolution of infectious conditions, yet unchecked secretion of inflammatory mediators can promote the dysregulated immune response implicated in COVID-19 complications. Overall, PEA supplementation produced anti-inflammatory effects in individuals recently diagnosed with COVID-19 who were nonhospitalized.

Post-Covid Olfactory Dysfunction (PCOD) is characterized by olfactory abnormalities, hyposmia, and anosmia, which are among the most often enduring symptoms in individuals who have recovered from SARS-CoV-2 infection. This disorder has been reported to persist in subsets of patients well after 12 months following infection, significantly affecting their quality of life. Despite the high prevalence of PCOD among patients who suffered from SARS-CoV-2 infection, specific therapeutic strategies are still limited. Among these, emerging evidence seems to indicate the administration of CoUltraPEALut, a combination of micronized Palmitoylethanolamide (PEA), an endogenous fatty acid amide, and Luteolin, a natural antioxidant flavonoid, as a viable therapy, especially when given as an adjuvant to olfactory training. Based on the above, a systematic review and a meta-analysis of the literature were conducted, with the aim of evaluating the efficacy of CoUltraPEALut as an addition to olfactory training (OT), in treating PCOD symptoms. Pubmed (MEDLINE), Embase (OVID), and Web of Science scientific databases were screened from the inception until 31 May 2023, and a total of 407 articles were recovered; only five of these studies (441 total patients between treated and control groups) were included in the systematic review. CoUltraPEALut demonstrated significant efficacy in the overall recovery of the olfactory function, compared to the conventional therapy, suggesting that it could represent a possible future adjuvant treatment for PCOD.

Background: Olfactory training is the only evidence-based treatment for post-viral olfactory dysfunction. Smell disorders after SARS-CoV-2 infection have been attributed to neuroinflammatory events within the olfactory bulb and the central nervous system. Therefore, targeting neuroinflammation is one potential strategy for promoting recovery from post-COVID-19 chronic olfactory dysfunction. Palmitoylethanolamide and luteolin (PEA-LUT) are candidate antiinflammatory/ neuroprotective agents. Objective: To investigate recovery of olfactory function in patients treated with PEA-LUT oral supplements plus olfactory training versus olfactory training plus placebo. Methods: Multicenter double-blinded randomized placebo-controlled clinical trial was held. Eligible subjects had prior COVID-19 and persistent olfactory impairment >6 months after follow-up SARS-CoV-2 negative testing, without prior history of olfactory dysfunction or other sinonasal disorders. Participants were randomized to daily oral supplementation with ultramicronized PEA-LUT 770 mg plus olfactory training (intervention group) or olfactory training with placebo (control). Sniffin’ Sticks assessments were used to test the patients at baseline and 90 days. Results: A total of 185 patients, including intervention (130) and control (55) were enrolled. The intervention group showed significantly greater improvement in olfactory threshold, discrimination, and identification scores compared to controls (p=0.0001). Overall, 92% of patients in the intervention group improved versus 42% of controls. Magnitude of recovery was significantly greater in the intervention group versus control (12.8 + 8.2 versus mean 3.2 + 3), with >10-fold higher prevalence of anosmia in control versus intervention groups at the 90-day endpoint. Conclusion: Among individuals with olfactory dysfunction post-COVID-19, combining PEA-LUT with olfactory training resulted in greater recovery of smell than olfactory training alone.