Breakthrough in Understanding Gulf War Syndrome: Impaired Mitochondria Identified as the Root Cause

Scientists at the University of California, San Diego have made a significant discovery regarding Gulf War Illness (GWI), a chronic condition that has plagued veterans of the 1991 Gulf War. Contrary to previous beliefs, the researchers found that impaired mitochondrial function, rather than inflammation, is the primary driver of this mysterious illness. This breakthrough could pave the way for improved treatment strategies not only for GWI but also for other conditions characterized by inflammation.

For over 30 years, GWI has affected approximately one-third of all veterans who served in the 1991 Gulf War, causing persistent symptoms such as fatigue, headaches, muscle aches, joint pain, diarrhea, insomnia, and cognitive impairment. The condition was thought to be triggered by exposure to environmental toxins, but its precise mechanism within the body has remained a subject of debate, hampering accurate diagnosis and treatment. The prevailing belief pointed to inflammation as the main culprit due to slightly elevated inflammatory markers in affected veterans compared to healthy individuals. However, an alternative hypothesis suggested that impaired mitochondria, the cellular organelles responsible for energy production, might be the true source of the symptoms.

In a recent study, scientists from UC San Diego School of Medicine directly examined mitochondrial impairment and inflammation in 36 individuals, including 19 veterans with GWI. The findings, published in Scientific Reports on July 12, 2023, challenge the long-standing assumption and indicate that impaired mitochondrial function, not inflammation, drives the symptoms of GWI. Therefore, future clinical interventions should prioritize addressing mitochondrial dysfunction.

Dr. Beatrice Golomb, the corresponding author of the study and a professor of medicine at UC San Diego School of Medicine, expressed the significance of this paradigm shift, stating, “This is a radical rethinking of the pathology of GWI. For veterans who have long struggled to get effective care, this discovery could be a real game changer.”

Veterans with Gulf War Illness have faced difficulties in receiving accurate diagnoses and suitable treatments, despite enduring symptoms for several decades.

To evaluate the roles of mitochondrial function and inflammation in GWI, the researchers obtained muscle biopsies from the study participants and assessed mitochondrial respiratory chain function (MRCF). Inflammation was evaluated by measuring high-sensitivity C-reactive protein (hsCRP) levels in participants’ blood, a common marker of peripheral inflammation.

By comparing this data with the participants’ GWI symptoms, the researchers discovered that the severity of symptoms correlated with the degree of mitochondrial impairment, rather than inflammation. Statistical analyses further revealed that 17 out of the 20 most common GWI symptoms were statistically linked to mitochondrial function, whereas only one symptom met this criterion for inflammation.

Additional analyses indicated that the extent of mitochondrial compromise in converting fat to energy was strongly associated with inflammation in GWI patients, but not in the control group. Reduced activity in this process, known as fatty acid oxidation, triggers cell death, leading to inflammation. Consequently, the researchers suggest that mitochondrial dysfunction may be the underlying reason for increased inflammation in GWI patients.

“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,” explained Dr. Golomb.

The researchers also observed that many GWI symptoms align with expected outcomes of mitochondrial dysfunction. For instance, impaired fatty acid oxidation due to mitochondrial dysfunction could explain the muscle aches and physical fatigue frequently experienced by GWI patients, as muscles rely heavily on fat for fuel. Conversely, brain symptoms in GWI, which are related to impairment in mitochondrial energy production using sugar as a fuel, align with the brain’s reliance on sugar for energy.

These findings have potential implications for various health conditions, including different forms of toxin exposure, aging, and even heart disease. Despite increased inflammation being a common characteristic of these conditions, they often do not respond well to anti-inflammatory drugs. Golomb and her colleagues propose that mitochondrial impairment may underlie these conditions, opening doors for novel therapeutic approaches.

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

The co-authors of the study include Roel Sanchez Baez, Jan M. Schilling, Mehul Dhanani, McKenzie J. Fannon, Brinton K. Berg, Bruce J. Miller, Pam R. Taub, and Hemal H. Patel, all from UC San Diego.

Frequently Asked Questions (FAQs) about Gulf War Syndrome

More about Gulf War Syndrome

• University of California, San Diego
• Scientific Reports
• Gulf War Illness – Department of Veterans Affairs