Effects of Ultramicronized Palmitoylethanolamide (um-PEA) in COVID-19 Early Stages: A Case–Control Study

Abstract

Ultramicronized palmitoylethanolamide (um-PEA), a compound with antioxidant, anti-inflammatory and neuroprotective properties, appears to be a potential adjuvant treatment for early stages of Coronavirus disease 2019 (COVID-19). In our study, we enrolled 90 patients with confirmed diagnosis of COVID-19 that were randomized into two groups, homogeneous for age, gender and BMI. The first group received oral supplementation based on um-PEA at a dose of 1800 mg/day for a total of 28 days; the second group was the control group (R.S. 73.20). At baseline (T0) and after 28 days of um-PEA treatment (T1), we monitored: routine laboratory parameters, inflammatory and oxidative stress (OS) biomarkers, lymphocytes subpopulation and COVID-19 serological response. At T1, the um-PEA-treated group presented a significant reduction in inflammation compared to the control group (CRP p = 0.007; IL-6 p = 0.0001; neutrophils to lymphocytes ratio p = 0.044). At T1, the controls showed a significant increase in OS compared to the treated group (FORT p = 0.05). At T1, the um-PEA group exhibited a significant decrease in D-dimer levels (p = 0.0001) and higher levels of IgG against SARS-CoV-2 (p = 0.0001) compared to the controls. Our data demonstrated, in a randomized clinical trial, the beneficial effects of um-PEA in both asymptomatic and mild-symptomatic patients related to reductions in inflammatory state, OS and coagulative cascade alterations.

Effect of Ultra-Micronized Palmitoylethanolamide and Luteolin on Olfaction and Memory in Patients with Long COVID: Results of a Longitudinal Study

“…PEA and LUT have potent neuroprotective and anti-inflammatory properties, and their bioavailability is significantly improved when administered in a micronized versus non-micronized form [ 22 ]. Ultra-micronization reduces particle size, improving absorption, metabolism, and therapeutic efficacy, as evidenced by several clinical studies [ 2 , 11 , 12 , 22 ]. PEA-LUT microgranules can be sublingually administered, which further enhances efficacy by minimizing the loss of activity from gastrointestinal degradation [ 23 ].…”

“…This finding, which is consistent with the neuroinflammatory hypothesis of long COVID symptoms [ 9 ], provides a rationale for targeting neuroinflammation to promote recovery. Palmitoylethanolamide and luteolin (PEA-LUT) have anti-inflammatory and neuroprotective properties [ 10 , 11 , 12 ]. In the present study, we investigated whether treatment with PEA-LUT, with or without olfactory training, was associated with an improvement in measures of olfactory function and mental clouding among patients affected by long COVID.…”

“…This finding, which is consistent with the neuroinflammatory hypothesis of long COVID symptoms [9], provides a rationale for targeting neuroinflammation to promote recovery. Palmitoylethanolamide and luteolin (PEA-LUT) have anti-inflammatory and neuroprotective properties [10][11][12].…”

Ultramicronized Palmitoylethanolamide and Luteolin: Drug Candidates in Post-COVID-19 Critical Illness Neuropathy and Positioning-Related Peripheral Nerve Injury of the Upper Extremity

“…36 ARDS is the clinical equivalent of diffuse alveolar damage, a histopathological picture consistently found in patients who died from severe COVID-19. 13 One us (LR) was among the first in the international medical literature to propose the use of PEA in COVID-19 and long-COVID 37 ; subsequently, further research supported this rationale, [38][39][40] and revealed also its utility in inhibiting the Nod-like receptor family pyrin domain containing 3 inflammasome expression in cultured murine alveolar macrophages stressed by the spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 41 as well as in inhibiting the entry of SARS-CoV-2, the etiological agent of COVID-19, into human cell lines by interacting with the spike protein and the angiotensin converting enzyme 2 receptors. 42 Moreover, the use of PEA in combination with luteolin improved olfactory dysfunction or mental clouding in a cohort of 69 patients (43 women, 26 men) with a mean age of 40.6 years affected by long-COVID, 43 and normalized γ-aminobutyric acid B -ergic activity and cortical plasticity in a further cohort of 39 long-COVID patients (26 women, 13 men) with a mean age of 49.9 years.…”

Parosmia COVID-19 Related Treated by a Combination of Olfactory Training and Ultramicronized PEA-LUT: A Prospective Randomized Controlled Trial

“…Several authors showed the efficacy of umPEA-LUT to fight the inflammation caused by COVID-19 infection [ 13 , 14 , 15 ], as well as the ability of the molecule of inhibiting the penetration of the SARS-CoV-2 virus protecting people from the infection [ 16 ].…”