Dietary Supplement Could Reduce Some Chronic Symptoms of Gulf War Illness.

Nearly one-third of the US military personnel deployed in the 1991 Gulf War continue to suffer from Gulf War Illness (GWI), a set of symptoms including chronic pain, fatigue, and memory impairment. Although the exact biology of GWI remains unknown, previous research suggests it is related to neuroinflammation caused by chemical exposure during the war.

Oleoylethanolamide (OEA), which is commonly used as a weight-loss supplement, could reduce GWI symptoms, according to a new study co-authored by a School of Public Health researcher in collaboration with Roskamp Institute investigators.

In the study, published in Scientific Reports, the investigators tested OEA in mice that had been exposed to the same chemicals as veterans with GWI. The mice showed reduced GWI symptoms, including improved memory and more energy.

“GWI is a chronic and debilitating disorder with no currently available targeted treatments,” says study co-author Kimberly Sullivan, research assistant professor of environmental health. “These results suggest that OEA has potential to be one of the first targeted treatments for veterans with GWI.”

The researchers first performed a pilot study which found an accumulation of very long chain fatty acids (VLCFA) in the blood plasma of veterans with GWI. In cells, VLCFAs are metabolized by small vesicles called peroxisomes, which break down fats and eliminate toxic material. When peroxisomes do not completely process VLCFAs, a buildup can trigger oxidative stress and increase the cells’ inflammatory responses. Previous studies have suggested that a disturbance in the peroxisomes metabolizing VLCFA is associated with the oxidative stress and inflammation seen in GWI, which could cause some of the disease’s cognitive and physical symptoms. OEA stimulates the proliferation of peroxisomes in cells, so the researchers hypothesized that it could help reduce this accumulation of VLCFAs and the associated symptoms.

To test this hypothesis, the researchers used a well-established mouse model of GWI, mice that had had an acute exposure to two of the chemicals that veterans with GWI were exposed to: the anti-nerve agent pyridostigmine bromide and the pesticide permethrin. To mirror the fact that the Gulf War ended over 27 years ago, for the mouse model the researchers waited five months after this chemical exposure before some of the GWI mice and some of the control mice received oral OEA treatment in their diets. These OEA mice continued to receive OEA for a total of six months, and the mice underwent a series of tests to assess their symptoms over the course of the study.

The GWI mice’s performance on a swim test declined over time, suggesting fatigue emerges as a GWI symptom with a time delay after chemical exposure. By the end of the six months, the GWI mice treated with OEA performed better on the swim test than the untreated GWI mice, but not as well as the control mice.

The untreated GWI mice took longer than the control mice to find their way through a maze that they had already explored, suggesting reduced learning and memory. GWI mice treated with OEA found their way faster than not only the untreated GWI mice but also the controls. This improved memory performance was consistent with the currently known effects of OEA on cognition, the authors wrote.

In the test of disinhibition, untreated GWI mice spent more time than the control mice in the open part of a maze rather than the covered part, suggesting that they were more disinhibited. GWI mice treated with OEA spent similar amounts of time in the open and sheltered parts of the maze as the control mice.

In biochemical and molecular analyses of the brain tissue of the mice, the researchers found more VLCFA and other related factors associated with oxidative stress and inflammation in the brains of the GWI mice, but that these were reduced in the GWI mice who had been treated with OEA.

“Gulf War veterans have waited many years for targeted treatments for their debilitating  disorder,” Sullivan says. “A follow-up treatment trial with Gulf War veterans is being planned.”

The study’s senior author was Laila Abdullah of the Roskamp Institute in Sarasota; Open University in Milton Keynes, UK; and James A. Haley Veterans’ Hospital in Tampa. The other co-authors were: Utsav Joshi, James Evans, Ross Joseph, Tanja Emmerich, Nicole Saltiel, Carlyn Lungmus, Heather Langlois, Sarah Oberlin, Chao Jin, Joseph Ojo, Benoit Mouzon, Daniel Paris, Michael Mullan, and Fiona Crawford of the Roskamp Institute; and Nancy Klimas of NOVA Southeastern University.

The work was funded by a Congressionally Directed Medical Research Programs (CDMRP) award and a Veterans Affairs Merit award to Abdullah, as well as contributions from the Roskamp Foundation and CDMRP funding to Sullivan.

—Michelle Samuels