Evidence map›Paper›PMID 35450527›Full record

Trial reportCurrent neuropharmacology2022

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.

Arianna Di Stadio, Luca D'Ascanio, Luigi Angelo Vaira, Elena Cantone, Pietro De Luca, Cristina Cingolani, Gaetano Motta, Giacomo De Riu, Federica Vitelli, Giuseppe Spriano and 5 more

Open access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Current neuropharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 5 pooled it
12.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 5 syntheses or guidelines pooled it, 102 citations in OpenAlex.

  1. Therapeutic effect of anti-neuroinflammatory supplement combined with olfactory training on post-covid olfactory dysfunction: a systematic review and meta-analysis.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026
    Pooled it
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  6. Persistent COVID-19 parosmia and olfactory loss post olfactory training: randomized clinical trial comparing central and peripheral-acting therapeutics.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2024
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  8. Treatment of COVID-19 olfactory dysfunction with olfactory training, palmitoylethanolamide with luteolin, or combined therapy: a blinded controlled multicenter randomized trial.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2023
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  10. Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABAClinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 2023
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  18. Patient-reported treatment outcomes in ME/CFS and long COVID.Proceedings of the National Academy of Sciences of the United States of America · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 8 institutions in 2 countries.

Arianna Di StadioOtolaryngology Department, University of Catania, Catania, Italy.
Luca D'AscanioOtolaryngology Department, AORMN, Fano- Pesaro, Italy.
Luigi Angelo VairaDepartment of Medical, Surgical and Experimental Sciences, Maxillofacial Surgery Operative Unit, University of Sassari, Sassari, Italy.
Elena CantoneDepartment of Neuroscience, Reproductive and Odontostomatological Sciences, Ear, Nose and Throat Section, Federico II University, Naples Italy.
Pietro De LucaOtolaryngology Department, University of Salerno, Salerno, Italy.
Cristina CingolaniOtolaryngology Department, AORMN, Fano- Pesaro, Italy.
Gaetano MottaDepartment of Neuroscience, Reproductive and Odontostomatological Sciences, Ear, Nose and Throat Section, Federico II University, Naples Italy.
Giacomo De RiuDepartment of Medical, Surgical and Experimental Sciences, Maxillofacial Surgery Operative Unit, University of Sassari, Sassari, Italy.
Federica VitelliOtolaryngology Department, AORMN, Fano- Pesaro, Italy.
Giuseppe SprianoDepartment of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, 4, 20090 Pieve Emanuele (MI), Italy.
Marco De VincentiisOtolaryngology Department, University La Sapienza, Rome, Italy.
Angelo CamaioniOtolaryngology Department, San-Giovanni Hospital, Rome, Italy.
Ignazio La MantiaOtolaryngology Department, University of Catania, Catania, Italy.
Fabio FerreliDepartment of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, 4, 20090 Pieve Emanuele (MI), Italy.
Michael J BrennerDepartment of Otolaryngology, University of Michigan Medical School, - Head and Neck Surgery, Ann Arbor (MI), USA.
Federico II University Hospital · ITUniversity of Catania · ITUniversity of Sassari · ITHumanitas University · ITIstituti di Ricovero e Cura a Carattere Scientifico · ITSapienza University of Rome · ITUniversity of Michigan–Ann Arbor · USUniversity of Salerno · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOlfactory 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.

objectiveTo investigate recovery of olfactory function in patients treated with PEA-LUT oral supplements plus olfactory training versus olfactory training plus placebo.

methodsMulticenter 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.

resultsA 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.

conclusionAmong individuals with olfactory dysfunction post-COVID-19, combining PEA-LUT with olfactory training resulted in greater recovery of smell than olfactory training alone.

Indexed as

COVID-19Olfaction DisordersAmidesDietary SupplementsEthanolaminesHumansLuteolinPalmitic AcidsSARS-CoV-2AmidesEthanolaminesLuteolinpalmidrolPalmitic Acidsanosmiaanti-inflammatorycoronavirusCOVID-19hyposmiaolfactionolfactory dysfunctionolfactory trainingSARS-CoV-2

Identifiers

PMID35450527
PMCPMC9886808
OpenAlexW4224254529

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.