Veterans and Gulf War mitochondria damage

Studies in the past 18 months have spotlighted the link between Gulf War Illness and veterans who suffered Gulf War mitochondria damage. Mitochondria are organelles found in large numbers found in most cells of the human body.

The most recent study, released in early September 2015, on its importance: “Multiple myeloma has been classified as exhibiting “limited or suggestive evidence” of an association with exposure to herbicides in Vietnam War veterans. Occupational studies have shown that other pesticides (ie, insecticides, herbicides, fungicides) are associated with excess risk of multiple myeloma and its precursor state, monoclonal gammopathy of undetermined significance (MGUS).” The study used 479 veterans of Operation Ranch Hand and 479 comparison veterans and found that, for the first time, there was direct evidence of greater mitochondrial damage in Gulf War veterans.

A look at each of the three major studies in the past 18 months:

Agent Orange Exposure and Monoclonal Gammopathy of Undetermined Significance

• Research Team: Rutgers University through Department of Veterans Affairs funding
• Findings Published: September 3, 2015 in JAMA
Conclusion: Veterans suffering from Gulf War illness have damaged mitochondria, which can lead to chronic fatigue, one of the main symptoms reported by Gulf War veterans. “The more we know about the type of (damage) and the more we can characterize the mitochondrial damage in these veterans, the better we can treat them,” said Michael Falvo, the study’s senior researcher and a faculty member of the VA War Related Illness and Injury Study Center in Orange, N.J. “The symptoms are so diverse and vary so much person to person that that’s been a challenging piece.” Gulf War illness (also known as Gulf War syndrome) is a multi-symptom disorder characterized by chronic fatigue, muscle pain and cognitive problems. While many believe that toxin exposure is to blame, and one study found a possible link to anti-nerve agent pills — toxic chemicals can damage mitochondria — the exact cause of the illness is still unknown. Falvo warned that while the study could help find better treatment, it was unlikely to uncover the root cause. “If I was a veteran experiencing Gulf War illness, I would want to know, too,” he said. “This many years after, that’s going to be a really difficult, if not impossible, thing to figure out.” The study, undertaken by Falvo and Rutgers Biomedical and Health Sciences doctoral researcher Yang Chen, was based on blood samples from more than 30 Gulf War veterans, including about two dozen who suffer from Gulf War illness. White blood cells were separated from the samples and researchers were able to study the mitochondrial DNA for evidence of damage. These are preliminary findings and the study will continue through the summer, with researchers hoping to present a final paper by the end of the year, Falvo said. A larger study will be needed to confirm the study’s findings, he said.
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Study: Coenzyme Q10 Helps Veterans Battle Gulf War Illness Symptoms

• Research Team: UC San Diego School of Medicine
• Findings Published: Nov. 1, 2014 in Neural Computation
• Conclusion: A high quality brand of coenzyme Q10 (CoQ10) – a compound commonly sold as a dietary supplement – provides  health benefits to persons suffering from Gulf War illness symptoms.  Forty-six United States Gulf War veterans participated in the randomized, double-blind, placebo-controlled study. Each veteran had been diagnosed with Gulf War illness. “Gulf War illness is not the same as post-traumatic stress disorder or traumatic brain injury, signature illnesses of later deployments, which are caused by psychological and mechanical injury, respectively,” said Beatrice Golomb, MD, PhD, professor of medicine at UC San Diego School of Medicine and principal investigator on the study. “Evidence instead links Gulf War illness to chemical exposures, such as pesticides or pills given to soldiers to protect them from possible nerve agents. These chemicals can damage mitochondria, which generate the energy our cells need to do their jobs. When these powerhouses of the cells are disrupted, it can produce symptoms compatible with those seen in Gulf War illness.” The connection to chemical and toxin exposures is fortified by evidence of mitochondrial problems in affected veterans, said Golomb, as well as evidence showing those veterans who became ill are significantly more likely than others to harbor genetic variants that render their enzymes less effective at detoxifying these chemicals. CoQ10 is a fat-soluble antioxidant made by the body to support basic cell functions, including directly assisting mitochondrial energy production. Over a course of three and a half months, the veterans in the study received a pill form of either CoQ10 or a placebo. Researchers found 80 percent of those who received 100mg of CoQ10 had improvement in physical function. The degree of improvement correlated to the degree in which CoQ10 levels in the blood increased. The researchers reported that Gulf War illness symptoms like headaches, fatigue with exertion, irritability, recall problems and muscle pain also improved.
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Mitochondrial Dysfunction in Gulf War Illness Revealed by 31Phosphorus Magnetic Resonance Spectroscopy: A Case-Control Study

• Research Team: UC San Diego School of Medicine
• Findings Published: March 27, 2014 issue of PLOS ONE
• Conclusion: Veterans of the 1990-91 Persian Gulf War who suffer from “Gulf War illness” have impaired function of mitochondria – the energy powerhouses of cells. The findings, published in the March 27, 2014 issue of PLOS ONE, could help lead to new treatments benefitting affected individuals – and to new ways of protecting servicepersons (and civilians) from similar problems in the future, said principal investigator Beatrice A. Golomb MD, PhD, professor of medicine. Golomb, with associate Hayley Koslik and Gavin Hamilton, PhD, a research scientist and magnetic resonance physicist, used the imaging technology to compare Gulf War veterans with diagnosed Gulf War illness to healthy controls. Cases were matched by age, sex and ethnicity. The technique used – 31-phosphorus magnetic resonance spectroscopy or 31P-MRS – reveals amounts of phosphorus-containing compounds in cells. Such compounds are important for cell energy production, in particular phosphocreatine or PCr, which declines in muscle cells during exercise. PCr recovery takes longer when mitochondrial function is impaired, and delayed recovery is recognized as a robust marker of mitochondrial dysfunction. Affected Gulf War veterans displayed significantly delayed PCr recovery after an exercise challenge. In fact, said Golomb, there was almost no overlap in the recovery times of Gulf War illness veterans compared to controls: All but one control participant had a recovery time-constant clustered under 31 seconds. In contrast, all but one Gulf Illness veteran had a recovery time-constant exceeding 35 seconds, with times ranging as high as 70 seconds. There were 14 participants in the study: seven Gulf War illness cases and seven matching controls. Golomb notes that the use of 1:1 matching markedly improves statistical “power,” allowing a smaller sample size. The separation between the two groups was “visibly striking, and the large average difference was statistically significant,” she said.
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Other Resources

Technical Abstract: Mechanisms of Mitochondrial Defects in Gulf War Syndrome (Download)
Gulf War Illness and the Health of Gulf War Veterans: Research Update and Recommendations, 2009-2013