Posted June 17, 2014
Beatrice Golomb, M.D., Ph.D., University of California, San Diego, California
Many veterans deployed in Operations Desert Shield and Desert Storm have since developed chronic multi-symptom health problems with a greater severity and multiplicity than Gulf War era veterans who were not deployed. These chronic multi-symptom health problems, often termed "Gulf War Illness" (GWI), are characterized by increased fatigue, exercise intolerance, cognitive difficulties, muscle pain and weakness, shortness of breath, gastrointestinal problems, sleep problems, behavior changes, and skin problems. GWI has been attributed to in-theatre exposure to a number of factors such as multiple vaccinations, chemical agent resistant coating paint, oil fires, permethrin-impregnated uniforms, and depleted uranium munitions. Current research however has focused substantially on exposures to cholinesterase inhibitors including organophosphate nerve gas residues, pyridostigmine bromide nerve agent pretreatment pills, and carbamate and organophosphate pesticides. These cholinesterase inhibitors work by preventing the breakdown of acetylcholine at nerve synapses; however, toxicity of these agents has also been shown to be mediated by oxidative stress and mitochondrial dysfunction.
Dr. Golomb and her team set out to objectively test for mitochondrial dysfunction using 31phosphorus magnetic resonance spectroscopy to examine the time it takes for muscle phosphocreatine (PCr) to recover to resting levels following exercise in Gulf War veterans with clinically diagnosed GWI compared to matched controls. The PCr recovery time constant called the "PCr-R" is widely considered to be a robust and practical index of mitochondrial functional status because PCr is a backup energy source that is depleted during exercise and recovery of PCr depends on mitochondrial production of adenosine triphosphate (ATP).
The participants in this study consisted of 14 veterans, including 7 cases meeting both the Centers for Disease Control and Prevention and "Kansas" definition for GWI, compared to 7 non-deployed controls. Participants were matched 1:1 on the basis of age, sex, and ethnicity. Following PCr assessment at rest, participants underwent 5 minutes of calf exercise. Following exercise, the PCr-R was measured in the case subjects and compared to those in matched controls. The results demonstrated that PCr-R was significantly prolonged in the cases compared to controls, indicating mitochondrial dysfunction is present in GWI.
This study was the first to show a connection between mitochondrial pathology and GWI, and these results are consistent with the observation by this group that coenzyme Q10, a primary endogenous antioxidant and electron carrier in the mitochondrial electron transport chain, is beneficial for the treatment of GWI. Moreover, the link between mitochondrial dysfunction and GWI provides further insight into the observation that veterans of the Gulf War have elevated rates of amyotrophic lateral sclerosis, a condition known to involve oxidative stress and mitochondrial dysfunction. Dr. Golomb plans to repeat this study in a larger number of veterans using additional methods for measuring mitochondrial function.
Publication:
Hayley J. Koslik, Gavin Hamilton and Beatrice A. Golomb. 2014. Mitochondrial dysfunction in Gulf War Illness revealed by 31 phosphorus magnetic resonance spectroscopy: A case-control study. PLoS ONE 9(3): e92887. doi:10.1371/journal.pone.0092887.
Links:
Public and Technical Abstracts: Gulf War Illness: Assessment of Bioenergetics in Brain and Muscle