The Effect of Oleoylethanolamide (OEA) Add-On Treatment on Inflammatory, Oxidative Stress, Lipid, and Biochemical Parameters in the Acute Ischemic Stroke Patients: Randomized Double-Blind Placebo-Controlled Study

Abstract

Background and Objective. There is a growing body of evidence for the efficacy of oleoylethanolamide (OEA) in patients with inflammatory disorders. The present randomized double-blind placebo-controlled study is aimed at evaluating the efficacy of OEA add-on treatment in patients with acute ischemic stroke (AIS). Methods. Sixty patients with a mean age of 68.60 ± 2.10 comprising 29 females (48.33%), who were admitted to an academic tertiary care facility within the first 12 hours poststroke symptoms onset or last known well (LKW), in case symptom onset time is not clear, were included in this study. AIS was confirmed based on a noncontrast head CT scan and also neurological symptoms. Patients were randomly and blindly assigned to OEA of 300 mg/day ( n = 20 ) or 600 mg/day ( n = 20 ) or placebo ( n = 20 ) in addition to the standard AIS treatment for three days. A blood sample was drawn at 12 hours from symptoms onset or LKW as the baseline followed by the second blood sample at 72 hours post symptoms onset or LKW. Blood samples were assessed for inflammatory and biochemical parameters, oxidative stress (OS) biomarkers, and lipid profile. Results. Compared to the baseline, there is a significant reduction in the urea, creatinine, triglyceride, high-density lipoprotein, cholesterol, alanine transaminase, total antioxidant capacity, malondialdehyde (MDA), total thiol groups (TTG), interleukin-6 (IL-6), and C-reactive protein levels on the follow-up blood testing in the OEA (300 mg/day) group. In patients receiving OEA (600 mg/day) treatment, there was only a significant reduction in the MDA level comparing baseline with follow-up blood testing. Also, the between-group analysis revealed a statistically significant difference between patients receiving OEA (300 mg/day) and placebo in terms of IL-6 and TTG level reduction when comparing them between baseline and follow-up blood testing. Conclusion. OEA in moderate dosage, 300 mg/day, add-on to the standard stroke treatment improves short-term inflammatory, OS, lipid, and biochemical parameters in patients with AIS. This effect might lead to a better long-term neurological prognosis.

Effects of oleoylethanolamide supplementation on inflammatory biomarkers, oxidative stress and antioxidant parameters of obese patients with NAFLD on a calorie-restricted diet: A randomized controlled trial

“…Moreover, a significant reduction in the expression levels of nuclear factor-kappa B (NF-kB) and IL-6 was observed in obese patients with NAFLD after OEA supplementation (Tutunchi et al, 2021). On the other hand, in the recent investigation by Sabahi et al (2022), OEA treatment (300 mg/ day) could improve the short-term inflammatory and oxidative stress status in patients with acute ischemic stroke. A significant reduction in serum levels of IL-1β, monocyte chemoattractant protein-1 (MCP-1), and TNF-α were also found by OEA supplementation (5 mg/kg) in alcohol intoxicated rats (Antón et al, 2017).…”

Contemplating IL‐6, a double‐edged sword cytokine: Which side to use for stroke pathology?

“…This antagonism did not, however, show any clinical benefit (ISRCTN74236229) 57 . Similarly, oleoylethanolamide shows reduced inflammation, oxidative stress, and dyslipidemia after ischemic stroke, but no functional recovery is reported 58 …”

“…57 Similarly, oleoylethanolamide shows reduced inflammation, oxidative stress, and dyslipidemia after ischemic stroke, but no functional recovery is reported. 58 Ongoing clinical trials are measuring IL-6 in relation to ischemic stroke prognosis (NCT05004389; NCT03297827), ischemic stroke treatment efficacy (NCT04705779), hemorrhagic stroke recovery using in-bed cycle ergometry (NCT04027049), and even IS and HS recovery following autologous mesenchymal stem cell therapy (NCT04063215).…”

Novel Multi-Antioxidant Approach for Ischemic Stroke Therapy Targeting the Role of Oxidative Stress

“…Oleoylethanolamide (OEA) is another compound with multiple antioxidant effects. This fatty acid has shown to reduce lipid peroxidation, prostaglandins, NO formation, and enhancing the GSH levels [ 101 ].…”