Gulf War Illness Caused by Mitochondrial Dysfunction, Not Inflammation

A recent study upends established theories about Gulf War Illness (GWI), a chronic condition affecting a third of veterans who served in the 1991 Gulf War. The study, led by researchers at the University of California San Diego School of Medicine, suggests the symptoms are driven by mitochondrial dysfunction, not inflammation as widely assumed.

Sufferers of GWI, still afflicted over three decades on, experience symptoms including fatigue, muscle aches, cognitive impairment, and other multisystem health issues. The underlying cause of these symptoms, which are believed to be linked to exposure to environmental toxins, has been under debate, complicating the illness’s diagnosis and treatment.

In the study published in Scientific Reports on July 12, 2023, the research team assessed mitochondrial impairment and inflammation in 36 individuals, including 19 veterans with GWI. The results revealed that impaired mitochondrial function was the principal driver of GWI symptoms.

“This is a radical rethinking of the pathology of GWI,” stated corresponding author Beatrice Golomb, MD, PhD, a professor of medicine at UC San Diego School of Medicine. “For veterans who have long struggled to get effective care, this discovery could be a real game changer.”

Mitochondrial function and inflammation were evaluated through muscle biopsies, which measured mitochondrial respiratory chain function (MRCF), and blood levels of high-sensitivity C-reactive protein (hsCRP), an inflammation marker. Statistical analyses found that 17 of the 20 most common GWI symptoms were linked to mitochondrial function. Only one of the 20 symptoms was related to inflammation.

Another analysis showed a strong correlation between the degree of mitochondrial compromise in converting fat to energy and the level of inflammation in GWI patients, but not in controls. This indicates that the mitochondrial dysfunction could trigger cell death leading to inflammation.

“Inflammation does appear to be linked to GWI, but our work suggests that it’s actually a side effect of the primary issue, which is impaired cell energy,” Golomb explained.

The study also suggests that the mitochondrial dysfunction may have potential implications for other health conditions such as aging, heart disease, and different forms of toxin exposure, which might not respond well to anti-inflammatory drugs.

“This is the first time that direct evidence for the mitochondrial hypothesis of GWI has been reported,” said Golomb. “We hope that it will lead to improved treatment plans for the veterans who have long struggled with this mysterious illness.”

This research received funding from the Department of Defense Congressionally Directed Medical Research Programs and the Veterans Administration.

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