Ultramicronized Palmitoylethanolamide and Luteolin Supplement Combined with Olfactory Training to Treat Post-COVID-19 Olfactory Impairment: A Multi-Center Double-Blinded Randomized Placebo- Controlled Clinical Trial-Reference-Cited by-同舟云学术

Ultramicronized Palmitoylethanolamide and Luteolin Supplement Combined with Olfactory Training to Treat Post-COVID-19 Olfactory Impairment: A Multi-Center Double-Blinded Randomized Placebo- Controlled Clinical Trial

Published:2022-10 Issue:10 Volume:20 Page:2001-2012
ISSN:1570-159X
Container-title:Current Neuropharmacology
language:en
Short-container-title:CN

Author:

Di Stadio Arianna¹,D’Ascanio Luca²,Vaira Luigi Angelo³⁴,Cantone Elena⁵,De Luca Pietro⁶,Cingolani Cristina²,Motta Gaetano⁵,De Riu Giacomo³,Vitelli Federica²,Spriano Giuseppe⁷⁸,De Vincentiis Marco⁹,Camaioni Angelo¹⁰,La Mantia Ignazio¹,Ferreli Fabio⁷⁸,Brenner Michael J.¹¹

Affiliation:

1. Otolaryngology Department, University of Catania, Catania, Italy

2. Otolaryngology Department, AORMN, Fano- Pesaro, Italy

3. Department of Medical, Surgical and Experimental Sciences, Maxillofacial Surgery Operative Unit, University of Sassari, Sassari, Italy

4. Department of Biomedical Sciences, PhD School of Biomedical Sciences, University of Sassari, Sassari, Italy

5. Department of Neuroscience, Reproductive and Odontostomatological Sciences, Ear, Nose and Throat Section, Federico II University, Naples Italy

6. Otolaryngology Department, University of Salerno, Salerno, Italy

7. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, 4, 20090 Pieve Emanuele (MI), Italy

8. Department of Otorhinolaryngology Head and Neck Surgery, Humanitas Clinical and Research Center -IRCCS-, Via Alessandro Manzoni, 56, 20089 Rozzano (MI), Italy

9. Otolaryngology Department, University La Sapienza, Rome, Italy

10. Otolaryngology Department, San-Giovanni Hospital, Rome, Italy

11. Department of Otolaryngology, University of Michigan Medical School, – Head and Neck Surgery, Ann Arbor (MI), USA

Abstract

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.

Publisher

Bentham Science Publishers Ltd.

Subject

Pharmacology (medical),Psychiatry and Mental health,Neurology (clinical),Neurology,Pharmacology,General Medicine

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