Successful Treatment of GWI with CoQ10: Implications for ME/CFS?

Beatrice A. Golomb has been researching Gulf War Illness for over two decades. In 1999 she published a paper, A Review of the Scientific Literature As It Pertains to Gulf War Illnesses; Pyridostigmine Bromide, implicating acetycholinesterase inhibitors as primary contributors to the development of GWI. (Fifteen years later, the Boston University School of Public Health confirmed her findings.) Golomb is the head of the UC San Diego Research Group, where she and other researchers study conditions related to oxidative stress and energy impairments.

Golomb recently finished a clinical trial using CoQ10 as a treatment for GWI. The results were impressive: 80% of treated veterans showed improved physical function after taking PharmaNord (Denmark) CoQ10 100 mg/day for 14 weeks. (You can read the abstract HERE.)

Oxidative stress and mitochondrial impairment are major players in ME/CFS, which is why there is so much overlap between the symptoms of GWI and ME/CFS. This is also why CoQ10 has been a staple in ME/CFS treatment arsenal since the late 1980s, when the Behans noted damage to the mitochondria in muscle tissues of ME patients in the UK.

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Coenzyme Q10 Helps Veterans Battle Gulf War Illness Symptoms

Press Release: UC San Diego, November 3, 2014. Roughly one-third of the 700,000 United States troops who fought in the 1990-1991 Persian Gulf War have subsequently developed a distinct set of chronic health problems, dubbed Gulf War illness. Their symptoms, from fatigue, muscle pain and weakness to decreased cognitive function and gastrointestinal and skin problems, persist decades after the conflict.

In a study published in the Nov. 1 issue of Neural Computation,  researchers at the University of California, San Diego School of Medicine report  that 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.

“The statistical significance of these benefits, despite the small sample size, underscores the large magnitude of the effects,” Golomb said. “Mounting evidence suggests findings in Gulf War illness are relevant to toxin-induced health problems in the civilian sector, so what we learn by studying health challenges of these veterans, will likely benefit others.”

Golomb and colleagues are seeking additional funding to test a more complete “mitochondrial cocktail,” which combines CoQ10 with additional nutrients that support cell energy and reduce oxidative damage to cells.

Co-authors include:  Matthew Allison, Sabrina Koperski, Hayley J. Koslik and Janis B. Richie, all at UC San Diego; and Sridevi Devaraj, Baylor College of Medicine/ Texas Children’s Hospital and Health Center.

Funding support for this research came, in part, from the Department of Defense.

Journal Reference: Beatrice A. Golomb, Matthew Allison, Sabrina Koperski, Hayley J. Koslik, Sridevi Devaraj, Janis B. Ritchie. Coenzyme Q10 Benefits Symptoms in Gulf War Veterans: Results of a Randomized Double-Blind Study. Neural Computation, 2014; 26 (11): 2594 DOI: 10.1162/NECO_a_00659

The IOM, GWI, and Plausible Deniability

The Boston University School of Public Health study on Gulf War Illness (see below) is interesting for a couple of reasons, one of which is the proposed use of intranasal insulin to reduce neuroinflammation in veterans with GWI. Given the recent study confirming brain inflammation in patients with ME/CFS, and the substantial overlap in symptoms between the two illnesses, it doesn't require a leap of the imagination to put two and two together. If intranasal insulin helps vets with GWI, it may very well help people with ME/CFS.

Another interesting point this study raises is the absolute disjuncture between scientific research and the IOM's position on GWI. In the IOM's 2013 report on GWI, it stated that "Specific etiological agents are unknown...There is a growing belief that no specific causal factor or agent will be identified."

Studies linking GWI to pyridostigmine have been in circulation since the 1990s (Abou-Donia MB, Lotti M and Moretto A.). A 1999 article, "Nerve Gas Antidote a Possible Cause of Gulf War Illness" (Charatan), cited a 385-page report written by Dr. Beatrice Golomb, professor of medicine at the University of California and physician at the Veterans Affairs Medical Center, San Diego which concluded that "pyridostigmine bromide cannot be ruled out as a possible contributor to the development of unexplained or undiagnosed illness in some Gulf war veterans." (Update published in 2008) This report was submitted to the IOM, which rejected pyridostigmine bromide as a cause of GWI, as it had done previously. ("The epidemiologic data do not provide evidence of a link between PB and chronic illness in Gulf War veterans." IOM report, Gulf War and Health: Volume 1. Depleted Uranium, Pyridostigmine Bromide, Sarin, and Vaccines ( 2000 ), page 252)

Fourteen years later, the IOM continued to deny a connection between pyridostigmine bromide and GWI. It also denied a connection between the Gulf War and GWI, renaming it "chronic multisymptom illness."

If nothing else, the IOM has been consistent in its ability to whitewash reality.

If the IOM was able to ignore a 385-page report sponsored by the Rand Corporation, two decades of published research, and the testimony of Gulf War vets (to whom the IOM expressed appreciation for their "willingness ... to share their experiences and thoughts") they will certainly be able to turn a blind eye to two decades of research on ME/CFS. Like the Gulf War vets, they will freely acknowledge our suffering, but will ultimately turn a deaf ear to the "experiences and thoughts" of ME/CFS patients and those who care for them.

The question I have is this: Is having the IOM appear to "listen" worth the inevitable outcome? At what point do we stop accepting validation of our feelings as a legitimate response to the critical problems of having no FDA-approved treatment, virtually no NIH funding, and a definition that will continue to relegate us to the no-man's land of waste basket diagnoses?
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Gulf War Illness: New Report Lauds Treatment Research, Confirms Toxic Causes

BU School of Public Health, April 28, 2014

Progress has been made toward understanding the physiological mechanisms that underlie Gulf War illness and identifying possible treatments, according to a report released Monday by a Congressionally mandated panel directed by a BU School of Public Health researcher.

Treatment research has increased significantly since 2008, and “early results provide encouraging signs that the treatment goals identified in the 2010 Institute of Medicine report are achievable,” the Research Advisory Committee on Gulf War Veterans’ Illnesses (RAC) said in a report presented to VA Secretary Eric Shinseki by the Committee’s scientific director, Roberta “Bobbie” White, chair of environmental health at BUSPH.

The Institute, part of the National Academies of Sciences, had forecast that “treatments, cures, and hopefully preventions” could likely be found with the right research.

The RAC report updates scientific research published since the Committee’s landmark report in 2008, which established that Gulf War illness was a real condition, affecting as many as 250,000 veterans of the 1990-91 Gulf War. The RAC Committee is composed of scientific experts and veterans.

“The conclusions of the 2008 RAC report had a substantial impact on scientific and clinical thinking about Gulf War illness, as well as the public acceptance of this disorder,” said White. The earlier report documented a number of studies that found evidence linking the illness to exposure to pesticides and pyridostigmine bromide (found in anti-nerve gas pills given to troops), as well as other toxic sources.

“Studies published since 2008 continue to support the conclusion that Gulf War illness is causally related to chemical exposures in the combat theater,” White said of the new report. “And many studies of the brain and central nervous system, using imaging, EEG and other objective measures of brain structure and function, add to the existing evidence that central nervous system dysfunction is a critical element in the disorder. Evidence also continues to point to immunological effects of Gulf War illness.”

Exposure to the nerve gas agents sarin and cyclosarin has been linked in several studies to changes in magnetic resonance imaging (MRI) that are associated with cognitive impairments — further supporting the nervous-system effects of those agents cited in the 2008 report.

“The Committee concludes that the evidence to date continues to point to alterations in central and autonomic nervous system, neuroendocrine, and immune system functions,” the report says.

Studies also continue to show that Gulf War illness is not associated with psychological stressors during the war, the panel said. Rates of PTSD and other psychiatric illnesses in Gulf War veterans are far below the rate of these disorders in veterans of other recent wars, and far below the rate of Gulf War illness.

In addition, the Committee said, new evidence has emerged suggesting that certain exposures may be linked to brain cancer in Gulf War veterans. Studies show that veterans who were most exposed to the release of nerve gas during the destruction of the Khamisiyah arms depot in Iraq have significantly elevated rates of death due to brain cancer.

Veterans who were exposed to the highest level of contaminants from oil well fires also have increased rates of brain cancer deaths, the report says.

The Committee encouraged studies exposing animals to toxic agents involved in Gulf War illness “because they can help to determine treatment targets in subgroups of veterans with specific exposures, for which there are known mechanistic pathways that cause illness and symptoms.”

In addition, “results from this work can be useful in protecting the health of future military personnel who will experience these exposures, as well as non-military populations with occupational or environmental exposures.”

The panel cited a number of “promising” treatment studies, including those testing certain dietary supplements, intranasal insulin, and continuous positive airway pressure to ease fatigue and pain and improve cognitive function.

A consortium of institutions led by BUSPH is studying markers in the blood and brain fluid, in addition to brain imaging (MRI and PET scans) and memory testing, to try to identify biomarkers of the condition. Studies also are planned on animals, to test initial treatments.

In a separate trial, BUSPH researcher Kim Sullivan and her colleagues are developing a possible treatment involving intranasal insulin, to target neuroinflammation. Researchers from the Boston VA Medical Center, the James J. Peters VA Medical Center in the Bronx, and the Icahn School of Medicine at Mount Sinai are involved in that trial, funded by a $1.7 million award from the Department of Defense.

While the RAC panel applauded an increase in the number of treatment studies funded by the Department of Defense’s Congressionally Directed Medical Research Program, it expressed grave concerns about a lack of research on other health problems and mortality among Gulf War veterans.

“Very little research” has been conducted to determine rates at which veterans have been affected by neurological diseases such as multiple sclerosis or Parkinson’s disease, cancers, and reproductive problems, the panel said.

“No comprehensive information has been published on the mortality experience of U.S. Gulf War era veterans after the year 2000,” according to the report.

Gulf War illness refers to the chronic symptoms that affect veterans of that conflict at markedly elevated rates, compared to other veterans’ groups and to the U.S. population as a whole. Symptoms can vary from person to person, but typically include some combination of widespread pain, headache, persistent problems with memory and thinking, fatigue, breathing problems, stomach and intestinal symptoms, and skin abnormalities.