Oleoylethanolamide supplementation improves mood and reduces fatigue in veterans with GWI in a 15-week randomized, double-blind, placebo-controlled exploratory clinical trial

TL;DR

A clinical trial found that oleoylethanolamide improved mood and reduced fatigue in veterans with Gulf War Illness, with no serious side effects.

Contribution

This is the first exploratory trial to demonstrate the safety and potential efficacy of OEA in treating Gulf War Illness symptoms.

Findings

OEA reduced fatigue and improved mood in veterans with Gulf War Illness.

OEA was well-tolerated with no serious adverse events reported.

No significant changes in cognitive performance or pain were observed.

Abstract

Gulf War Illness (GWI) affects 32% of Veterans from the 1990–1991 Gulf War. It is characterized by fatigue, mood disturbances, pain and cognitive decrements, with no FDA-approved treatment. This exploratory randomized, double-blind, placebo-controlled trial evaluated the safety and efficacy of oleoylethanolamide (OEA) supplementation in 52 Veterans with GWI (mean age 59 ± 5 SD, 94% males and 79% White). Participants received 200 mg of OEA twice daily or a matching placebo for 10 weeks, followed by a 5-week open-label OEA extension. Outcomes included the Multidimensional Fatigue Inventory (MFI-20), abbreviated Profile of Mood States (POMS), Short-Form McGill Pain Questionnaire, Veterans RAND 36-Item Health Survey (SF-36 V), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and CNS Vital Signs Test, administered at baseline and 10- and 15-weeks. A main effect of OEA for reducing fatigue (MFI-20, p ≤ 0.05) and improving the total mood disturbances score (POMS, p ≤ 0.05) was observed. Participants on OEA reported increased energy, emotional well-being, and social functioning (SF-36 V, p ≤ 0.05). No changes were seen in cognitive performance or pain. Oleoylethanolamide was well-tolerated with no serious adverse events. In summary, OEA was safe and improved fatigue and mood in Veterans with GWI. Larger trials are needed to confirm these benefits.

Registered under ClinicalTrials.gov Identifier no. NCT05252949 (first posted date: 23/02/2022).

The online version contains supplementary material available at 10.1038/s41598-026-35168-3.

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