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
Author information is not available.
What this study found
PEA-LUT plus olfactory training yielded superior olfactory recovery versus olfactory training with placebo after 90 days. In the intervention group, 92% improved on TDI versus 42% in controls (p=0.0001). Mean TDI increased from 20.6±7.9 to 29.8±7.5 in the intervention group (p<0.001); controls increased from 18.2±7.9 to 19.5±7.3 (p=0.4). Normal olfactory function (TDI>31) at 90 days occurred in 56% of the intervention group versus 10% of controls. Magnitude of recovery (>5 points) occurred in 66.7% vs 26.1%. Authors conclude the combination accelerates and enhances smell recovery, likely by…
- Study & population
- Multicenter, double-blind randomized placebo-controlled trial at three centers (Fano, Naples, Sassari).
- Intervention
- PEA-LUT 770 mg daily (Palmitoylethanolamide 700 mg + Luteolin 70 mg) taken orally 5–10 minutes before breakfast; duration: 90 days.
- Key limitation
- No inflammatory biomarkers or pharmacokinetic data; unable to separate PEA-LUT effect from olfactory training; unequal 2:1 randomization; relatively young cohort; 90-day follow-up; potential placebo effects; limited generalizability to older populations.
View source
Open PDFOriginal 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 anti-inflammatory/ 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. Clinical Trial Registration: (Italian; Clinicaltrials.gov number: NCT04853836)