A newly released study by a leading Gulf War Illness researcher, Dr. Beatrice Golomb of the University of California-San Diego, has shown objective evidence of the mitochondrial dysfunction implied by earlier Gulf War illness research, including a study that found Coenzyme Q10 (CoQ10) to be effective in treating some GWI symptoms. Mitochondria, the powerhouses of the human body's cells, use CoQ10 to generate energy.
It speaks volumes the fact that the proposal for this study was
peer-reviewed, scored high enough to be funded and then was selected for
funding in a steep competition.... that publication of the study's results were
in a leading peer-reviewed scientific journal... which helps back up the
researcher's assertion that the matching of controls and statistical
significance of all the ill veterans in the study having the marker but none of
the health, carefully matched controls having it (and in fact they all came out
the same)....
For those who have been following GWI research, the results of
this study aren't entirely surprising. The fact that CoQ10 was shown to be effective in
treating some GWI symptoms (for every one of the study subjects!) by itself
implied mitochondrial dysfunction. This study took aim at that component of GWI
(one of several major hypothesized components in the currently prevailing
theories of GWI pathobiology), and found a probable biomarker right where earlier
research suggested it would be.
While VA still doesn't provide CoQ10 as a formulary item, it
should. For Gulf War veterans with Gulf War Illness like me, CoQ10 (in combination with other neutraceutical
anti-inflammatories and anti-oxidants) makes a big difference in reducing
symptoms and increasing energy.
The PLOS One journal article is here, and the archived text of several reports about the study is below. 1) Newsweek; 2) Neuroscience; 3) Discover Magazine; 4) UCSD Press Release; 5) MedicalResearch.com.
-A.H.
***
1) SOURCE: Newsweek, Rob Verger reporting (3/29/2014)
http://www.newsweek.com/sick-soliders-gulf-war-illness-clue-mystery-their-cells-238850
ARCHIVED TEXT:
For Soldiers With Gulf War Illness, a Clue to the Mystery in Their Cells
By Rob Verger
Filed: 3/29/14 at 6:53 AM
PHOTOE: Doctors found changes in mitochondria of veterans of the first Gulf War suffering from a variety of mysterious aliments Andy Clark / Reuters
Filed Under: Tech & Science, Gulf War Illness, First Gulf War, Veterans, Studies, Health and Science
As a kid, Adam Such knew he wanted to join the military when he grew up. And after graduating from West Point in 1989, he went on to have a career that included 17 years in special operations, which he discovered he “had a passion” for, he says. Such served in the first Gulf War, the 2003 Iraq War, and other places, too. In Fallujah, Iraq, in 2004, his helicopter was shot down, resulting in a broken back.
But in the years after his time in the first Gulf War, he began to realize that something didn’t feel right about his health. “By the mid-90s,” he recalled, “I absolutely recognized a significant degradation in my stamina, my focus, my concentration; the worst part was what’s now termed fibromyalgia… because it’s everywhere.” His symptoms also included joint pain. But, he says, he was a typical soldier: you tough through things, and you don’t look for “externals” to explain your problems. He had thought of the tiredness as what he calls “the post-deployment fatigue”—just a result of pushing his body—but now he knows better: eventually he was diagnosed with Gulf War Illness.
Once known as Gulf War Syndrome, Gulf War Illness is now a diagnosis recognized by the Veterans Administration. But it remains a perplexing sickness. It can display as an array of seemingly unrelated symptoms, including headache, gastrointestinal problems, pain, and fatigue — and its onset can be many years after exposure. Roberta White, a professor at Boston University’s School of Public Health, calls the disease a “complex illness” as the underlying biological processes are not precisely clear.
More than 700,000 troops were deployed in the Gulf War, and the Department of Defense estimates that “as many as 200,000 veterans” of that conflict might be affected. Treatment is difficult, and not all veterans show the same symptoms, with the same severity, nor respond to treatments in the same way.
And assigning blame is difficult. It’s nearly impossible to figure out whether exposure to a specific substance can cause any given case of Gulf War Illness. However, many vets remember things from their tours that didn’t—and still don’t—sit right. One Gulf War veteran, Melissa Forsythe (a retired colonel who now is the program manager for the Department of Defense Gulf War Illness Research Program) recalls the burning oil wells: “you could taste it, in your mouth,” she tells Newsweek. “If you blew your nose, it came out black.” Forsythe knows of another veteran who was in a recently-vacated Iraqi bunker when he noticed a distinct scent: “geraniums and onions.” That was probably from mustard gas and another nerve agent, she says. Another veteran, Andy Berdy, a now-retired colonel who commanded a battalion in the war, spoke of feeling “tired all the time” after he retired, and would experience “momentary blackouts.” As for the causes of his illness, “Something happened in our deployment in Desert Storm,” he says. Berdy brought up a specific anti-nerve-agent pill he took (which in the middle of their deployment they were urgently told to stop taking) or as well as agricultural chemicals he was exposed to after spending weeks in fox holes dug into soil near the Euphrates River.
One physician thinks she’s found an important clue inside the cells of stricken vets. Dr. Beatrice Golomb, a medical doctor and researcher at the University of California, San Diego School of Medicine, suspected that the problem might be in the mitochondria that are found in the body’s cells.
You may remember mitochondria from high school biology: they are the way the body produces energy. Some of the “classic symptoms” of Gulf War Illness, like fatigue, match perfectly with the symptoms of a person with mitochondrial disorder, Golomb says. A person with mitochondrial dysfunction could feel tired, have trouble exercising, have gastrointestinal problems or even cognitive problems—just like with Gulf War Illness. Other factors make it a likely fit, too.
Golomb matched seven veterans who had Gulf War Illness with seven healthy controls of a similar profile. To measure mitochondrial function, she focused on a substance called phosphocreatine, which she describes as an “energy backup.” Both the veterans and the healthy controls exercised, and Golomb’s team measured the phosphocreatine recovery afterwards. She found that in six of the seven pairs, the recovery for the veterans was significantly delayed compared to the controls—pointing a finger at mitochondrial dysfunction.
That alone doesn’t mean their health problems were caused by the events of Gulf War, since mitochondrial dysfunction can be caused by any number of things. However, according to Golomb, “We know that mitochondrial dysfunction is triggered by some of the classes of chemicals that show the strongest epidemiological link to Gulf War Illness.” In other words, the problems she found are linked to things those vets probably breathed in, swallowed, or otherwise put in their bodies back in the 90s. The results of her study were just published in the journal PLOS One.
Experts suspect a variety of toxins could be linked to Gulf War Illness—from pesticides to the anthrax vaccine—but one likely culprit, Golomb says, is something that wasn’t an enemy weapon, or even an accidentally released chemical: the PB pill. The PB pill was given to troops by the U.S. Armed Forces in case of possible exposure to nerve agents—it was a preventative. The cure may have made them sick.
The study is too small to draw big conclusions from, says Lea Steele, the director of the Veterans’ Health Research Program at Baylor University. “It’s potentially very important, especially if larger studies validate what Dr. Golomb’s team found. Bottom line on this illness is that people have been sick so long. And we are beginning to understand the mechanisms of the illness, but we really haven’t identified effective treatments that we know can apply to a lot of people.”
Adam Such retired in 2009 with the rank of lieutenant colonel. His health was part of the reason—he needed surgeries after being shot down in 2004—and he was a single dad, too. Even given his health issues, he says he wouldn’t change his career. “For the service, I volunteered to do it. I’d do it again in a heartbeat,” he says. But he feels for other veterans who might not have the resources or support he does. “That’s where you see the emotions come out with me, where I become very adamant about our obligation to treat and take care a lot of these young men and women who willingly went and served.”
As for helping veterans who are suffering from Gulf War Illness, Golomb says that “there are potential treatment implications” based on the results of this small study. She’s still working on it. “I think there will be treatment strategies that will clearly” benefit sick vets, she says. Still, she added: “It will still be a challenge to generate a complete cure.”
****
2) SOURCE: Neuroscience News, March 28, 2014
http://neurosciencenews.com/mitochondria-function-gulf-war-illness-902/
ARCHIVED TEXT:
Gulf War Illness Not in Veterans’ Heads, But in Their Mitochondria
Researchers at the UC San Diego School of Medicine have demonstrated for the first time that 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.
Impaired mitochondrial function accounts for numerous features of Gulf War illness, including symptoms that have been viewed as perplexing or paradoxical. This is a diagram of a mitochondrion. The image is not connected to the research and is used for illustrative purposes only. Credit Kelvinsong.
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.
Golomb noted that impaired mitochondrial function accounts for numerous features of Gulf War illness, including symptoms that have been viewed as perplexing or paradoxical.
“The classic presentation for mitochondrial illness involves multiple symptoms spanning many domains, similar to what we see in Gulf War illness. These classically include fatigue, cognitive and other brain-related challenges, muscle problems and exercise intolerance, with neurological and gastrointestinal problems also common.”
There are other similarities between patients with mitochondrial dysfunction and those suffering from Gulf War illness: Additional symptoms appear in smaller subsets of patients; varying patterns of symptoms and severity among individuals; different latency periods across symptoms, or times when symptoms first appear; routine blood tests that appear normal.
“Some have sought to ascribe Gulf War illness to stress,” said Golomb, “but stress has proven not to be an independent predictor of the condition. On the other hand, Gulf veterans are known to have been widely exposed to acetylcholinesterase inhibitors, a chemical class found in organophosphate and carbamate pesticides, nerve gas and nerve gas pre-treatment pills given to troops.
“These inhibitors have known mitochondrial toxicity and generally show the strongest and most consistent relationship to predicting Gulf War illness. Mitochondrial problems account for which exposures relate to Gulf War illness, which symptoms predominate, how Gulf War illness symptoms manifest themselves, what objective tests have been altered, and why routine blood tests have not been useful.”
Notes about this neurology and genetics research
Funding for this research came, in part, from a UC San Diego Academic Senate Award and the U.S. Department of Defense.
Contact: Scott LaFee – UCSD
Source: UCSD press release
Image Source: The image is credited Kelvinsong. The author has released the image into the public domain.
Original Research: Full open access research for “Mitochondrial Dysfunction in Gulf War Illness Revealed by 31Phosphorus Magnetic Resonance Spectroscopy: A Case-Control Study” by Hayley J. Koslik, Gavin Hamilton, and Beatrice A. Golomb in PLOS ONE. Published online March 27 2014 doi:10.1371/journal.pone.0092887
Source: UCSD press release
Image Source: The image is credited Kelvinsong. The author has released the image into the public domain.
Original Research: Full open access research for “Mitochondrial Dysfunction in Gulf War Illness Revealed by 31Phosphorus Magnetic Resonance Spectroscopy: A Case-Control Study” by Hayley J. Koslik, Gavin Hamilton, and Beatrice A. Golomb in PLOS ONE. Published online March 27 2014 doi:10.1371/journal.pone.0092887
Open Access Neuroscience Abstract
Mitochondrial Dysfunction in Gulf War Illness Revealed by 31Phosphorus Magnetic Resonance Spectroscopy: A Case-Control Study
Approximately 1/3 of 1990-1 Gulf War veterans developed chronic multisymptom health problems. Implicated exposures bear mechanisms that adversely affect mitochondria. Symptoms emphasize fatigue, cognition and muscle (brain and muscle are aerobically demanding); with protean additional domains affected, compatible with mitochondrial impairment. Recent evidence supports treatments targeting cell bioenergetics (coenzyme10) to benefit Gulf War illness symptoms. However, no evidence has directly documented mitochondrial or bioenergetic impairment in Gulf War illness.
“Mitochondrial Dysfunction in Gulf War Illness Revealed by 31Phosphorus Magnetic Resonance Spectroscopy: A Case-Control Study” by Hayley J. Koslik, Gavin Hamilton, and Beatrice A. Golomb in PLOS ONE, March 27 2014 doi:10.1371/journal.pone.0092887
****
3) SOURCE: Discover Magazine, Gemma Tarlach reporting, March, 27, 2014
ARCHIVED TEXT:
Doctors have struggled for decades to find a cause for a host of debilitating health problems experienced by veterans of the 1990-91 Persian Gulf War. As many as a third of servicemen and women deployed overseas during the conflict have complained of symptoms such as chronic headaches and crippling fatigue.
Much of the most promising recent research, such as a 2013 study on pain processing, has focused on the brain, identifying significant differences between Gulf War syndrome (GWS) sufferers and the general population.
For the first time, however, researchers have now shown that individuals with GWS have impaired cellular components called mitochondria throughout their bodies.
Mitochondria on the Mind
Mitochondria, present in nearly all of our cells, convert energy into useable forms and are involved in both cell division and cell death. Previous research has established that mitochondrial impairment can lead to brain, heart and endocrinal damage, among other serious problems. Mitochondrial damage has been suggested as a potential cause of GWS but never previously proven in individuals diagnosed with the syndrome.
Only 14 participants took part in the study: seven veterans diagnosed with Gulf War Syndrome and a control group of seven healthy civilians. Acknowledging the small sample size, the researchers say the results were still significant because GWS and control individuals were matched 1:1 for age, sex and ethnicity.
Delayed Recovery
Scientists used an imaging technique to find a chemical called phosphocreatine (PCr). PCr, which is regulated by mitochondria, is depleted by exercise. When a cell’s mitochondria are impaired, it takes longer for PCr levels to return to normal. Measuring PCr levels has been an accepted way of diagnosing a range of mitochondrial diseases.
Researchers measured PCr levels before, during and after study participants exercised by depressing a foot pedal for five minutes. PCr recovery time for the GWS group was significantly longer than for the control group, with little overlap between groups. In fact, noted researchers, only one outlier member of the control group had a PCr recovery time in the same range as that of the GWS group. While 6 of the 7 control group members had PCr recovery rates of 31 seconds or less, members of the GWS group had PCr recovery rates of 35-70 seconds.
Establishing a link between impaired mitochondrial function and GWS is significant because mitochondrial disease is often difficult to diagnose — an individual’s blood test could appear normal, for example — and because it could cause a broad range of symptoms like GWS is known to do. In addition, many veterans diagnosed with GWS were exposed to chemicals, such as pesticides and nerve gas, that are known to damage mitochondria.
The findings, which appeared today in the open-access online journal PLoS One, could lead both to more accurate diagnosis of GWS and possible therapies.
Photo credit: Fæ/Wikimedia Commons
MORE ABOUT: PERSONAL HEALTH
***
4) SOURCE: UCSD Press Release, 3/27/2014
ARCHIVED TEXT:
News Release
Date: March 27, 2014
Gulf War Illness Not in Veterans’ Heads, But in Their Mitochondria
Researchers at the UC San Diego School of Medicine have demonstrated for the first time that 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.
Golomb noted that impaired mitochondrial function accounts for numerous features of Gulf War illness, including symptoms that have been viewed as perplexing or paradoxical.
“The classic presentation for mitochondrial illness involves multiple symptoms spanning many domains, similar to what we see in Gulf War illness. These classically include fatigue, cognitive and other brain-related challenges, muscle problems and exercise intolerance, with neurological and gastrointestinal problems also common.”
There are other similarities between patients with mitochondrial dysfunction and those suffering from Gulf War illness: Additional symptoms appear in smaller subsets of patients; varying patterns of symptoms and severity among individuals; different latency periods across symptoms, or times when symptoms first appear; routine blood tests that appear normal.
“Some have sought to ascribe Gulf War illness to stress,” said Golomb, “but stress has proven not to be an independent predictor of the condition. On the other hand, Gulf veterans are known to have been widely exposed to acetylcholinesterase inhibitors, a chemical class found in organophosphate and carbamate pesticides, nerve gas and nerve gas pre-treatment pills given to troops.
“These inhibitors have known mitochondrial toxicity and generally show the strongest and most consistent relationship to predicting Gulf War illness. Mitochondrial problems account for which exposures relate to Gulf War illness, which symptoms predominate, how Gulf War illness symptoms manifest themselves, what objective tests have been altered, and why routine blood tests have not been useful.”
Funding for this research came, in part, from a UC San Diego Academic Senate Award and the U.S. Department of Defense.
# # #
Media contact: Scott LaFee, 619-543-6163, slafee@ucsd.edu
****
SOURCE: ProHealth
http://www.prohealth.com/library/showarticle.cfm?libid=18852
Mitochondrial Dysfunction in Gulf War Illness Revealed by 31Phosphorus Magnetic Resonance Spectroscopy: A Case-Control Study
By Hayley J. Koslik et al.
Abstract
Background: Approximately 1/3 of 1990-1 Gulf War veterans developed chronic multisymptom health problems. Implicated exposures bear mechanisms that adversely affect mitochondria. Symptoms emphasize fatigue, cognition and muscle (brain and muscle are aerobically demanding); with protean additional domains affected, compatible with mitochondrial impairment. Recent evidence supports treatments targeting cell bioenergetics (coenzyme10) to benefit Gulf War illness symptoms. However, no evidence has directly documented mitochondrial or bioenergetic impairment in Gulf War illness.
Objective: We sought to objectively assess for mitochondrial dysfunction, examining post-exercise phosphocreatine-recovery time constant (PCr-R) using 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS), in Gulf War veterans with Gulf War illness compared to matched healthy controls. PCr-R has been described as a "robust and practical" index of mitochondrial status.
Design and Participants: Case-control study from 2012-2013. Fourteen community-dwelling Gulf War veterans and matched controls from the San Diego area comprised 7 men meeting CDC and Kansas criteria for Gulf War illness, and 7 non-deployed healthy controls matched 1:1 to cases on age, sex, and ethnicity.
Outcome Measure: Calf muscle phosphocreatine was evaluated by 31P-MRS at rest, through 5 minutes of foot pedal depression exercise, and in recovery, to assess PCr-R. Paired t-tests compared cases to matched controls.
Results: PCr-R was significantly prolonged in Gulf War illness cases vs their matched controls: control values, mean±SD, 29.0±8.7 seconds; case values 46.1±18.0 seconds; difference 17.1±14.9 seconds; p = 0.023. PCr-R was longer for cases relative to their matched controls for all but one pair; moreover while values clustered under 31 seconds for all but one control, they exceeded 35 seconds (with a spread up to 70 seconds) for all but one case.
Discussion: These data provide the first direct evidence supporting mitochondrial dysfunction in Gulf War illness. Findings merit replication in a larger study and/or corroboration with additional mitochondrial assessment tools.
Source: Hayley J. Koslik, Gavin Hamilton, Beatrice A. Golomb. PLOSONE. Published: March 27, 2014 DOI: 10.1371/journal.pone.0092887
Abstract
Background: Approximately 1/3 of 1990-1 Gulf War veterans developed chronic multisymptom health problems. Implicated exposures bear mechanisms that adversely affect mitochondria. Symptoms emphasize fatigue, cognition and muscle (brain and muscle are aerobically demanding); with protean additional domains affected, compatible with mitochondrial impairment. Recent evidence supports treatments targeting cell bioenergetics (coenzyme10) to benefit Gulf War illness symptoms. However, no evidence has directly documented mitochondrial or bioenergetic impairment in Gulf War illness.
Objective: We sought to objectively assess for mitochondrial dysfunction, examining post-exercise phosphocreatine-recovery time constant (PCr-R) using 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS), in Gulf War veterans with Gulf War illness compared to matched healthy controls. PCr-R has been described as a "robust and practical" index of mitochondrial status.
Design and Participants: Case-control study from 2012-2013. Fourteen community-dwelling Gulf War veterans and matched controls from the San Diego area comprised 7 men meeting CDC and Kansas criteria for Gulf War illness, and 7 non-deployed healthy controls matched 1:1 to cases on age, sex, and ethnicity.
Outcome Measure: Calf muscle phosphocreatine was evaluated by 31P-MRS at rest, through 5 minutes of foot pedal depression exercise, and in recovery, to assess PCr-R. Paired t-tests compared cases to matched controls.
Results: PCr-R was significantly prolonged in Gulf War illness cases vs their matched controls: control values, mean±SD, 29.0±8.7 seconds; case values 46.1±18.0 seconds; difference 17.1±14.9 seconds; p = 0.023. PCr-R was longer for cases relative to their matched controls for all but one pair; moreover while values clustered under 31 seconds for all but one control, they exceeded 35 seconds (with a spread up to 70 seconds) for all but one case.
Discussion: These data provide the first direct evidence supporting mitochondrial dysfunction in Gulf War illness. Findings merit replication in a larger study and/or corroboration with additional mitochondrial assessment tools.
Source: Hayley J. Koslik, Gavin Hamilton, Beatrice A. Golomb. PLOSONE. Published: March 27, 2014 DOI: 10.1371/journal.pone.0092887
*****
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SOURCE: MedicalResearch.com, Dr. Marie Benz interviewing
ARCHIVED TEXT:
Gulf War Illness May Be Due to Mitochondrial Damage from Toxin Exposures
MedicalResearch.com Interview with:Beatrice A. Golomb MD, PhD
Professor of Medicine
Family and Preventive Medicine
University of California, San Diego
MedicalResearch.com: What are the main findings of the study?
Dr. Golomb: The main finding is that veterans with Gulf War illness have bioenergetic defects — dysfunction of mitochondria, the energy producing elements of cells — that is evident in comparing affected veterans to matched healthy controls.
An estimated 1/4 to 1/3 of the ~700,000 US veterans from the 1990-1 Gulf War developed chronic multisymptom health problems that entail fatigue, cognitive and other CNS problems, muscle pain, weakness and exercise intolerance, with high rates of gastrointestinal (especially diarrhea) and neurological problems, and other symptoms – as well as autonomic dysfunction. Evidence suggests these problems have not abated with time. Veterans from other nations that have conducted epidemiological studies, including the UK, Canada, and Australia, also show elevated rates of problems.
MedicalResearch.com: Were any of the findings unexpected?
Dr. Golomb: The findings are unquestionably new, and they will be unexpected to many or most. To my knowledge no prior study has documented (or looked for) mitochondrial dysfunction in Gulf War illness.
I have urged research to examine this at least since 2002, in the earliest meetings of the Research Advisory Committee on Gulf War Veterans’ Illnesses, for which I was the inaugural Scientific Director. At that time, though, only researchers employed by the VA, with at least 5/8 time appointments, were eligible to apply for research funds to study Gulf War illness, which were administered only through the VA. (So, many with promising ideas could not apply for funding.)*
This research was funded through the Department of Defense and their Congressionally Directed Medical Research Program, or CDMRP. Congress appropriated additional funds for research in this area to be administered through the Department of Defense, open to all investigators. In my view and that of many veterans, that research program has done a superior job in directing funds toward projects that have prospects to actually help understand and treat this condition. Reasons for this include the apparent will to do the right thing; and, in addition to knowledgeable scientific reviewers, their inclusion of a “relevancy review” by the most important stakeholder — affected Gulf War veterans.
So, the idea that mitochondrial dysfunction might be a major factor if not the key to understanding Gulf War illness was what motivated the study. But one can never be sure whether one’s hypotheses will be borne out.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Golomb: This has potential to be a watershed. Findings from this study support a mechanism that accounts remarkably for the accumulated evidence related to Gulf War veterans (as no other hypothesized mechanism has). It fits with information on what exposures relate to Gulf War illness, how the symptoms behave, which objective markers are and are not abnormal, and what other conditions are observed.
I. The exposures that have shown the strongest and most consistent body of evidence connecting them to Gulf War illness, are powerful oxidative stressors that have been shown to confer mitochondrial toxicity in animals. These are acetylcholinesterase inhibitors or “AChEi.”
Veterans were exposedto AChEi via the pyridostigmine bromide nerve agent pretreatment pills given to an estimated 250,000 US troops; which are carbamate AChEis. They were exposed via carbamate and organophosphate pesticides which were used aggressively and in some instances overzealously in efforts to protect against insect vectors of disease (with overexposure for some acknowedged by the DoD). They were exposed via organophosphate nerve gas to which servicepersons were exposed in association with demolition of an Iraqi munitions depot (one for sure, others unconfirmed).
II. The characteristics of symptoms are compatible in numerous particulars with mitochondrial dysfunction, including features that have been deemed paradoxical, or have even been wrongly cited as implying toxic exposures cannot be responsible. These are:
a. Multiplicity of symptom that are protean and span many domains. Around the same number of Gulf deployed and nondeployed have 1 or 2 mild symptoms (as studied by Lea Steele, in Kansas veterans). What is different and “unique” among Gulf deployed personnel, is that there is a large distinctive group who showed symptoms spanning at least 3 of 6 assessed domains (fatigue-sleep, pain, neurological, gastrointestinal, respiratory-breathing, dermatologic), that were of at least moderate severity (not mild), and/or involved more than one symptom within the domain. This multiplicity is also characteristic of mitochondrial illness.
b. The specifics of the symptoms differ from person to person This is also characteristic of mitochondrial illness.
c. Symptoms are dominated by fatigue, cognitive/CNS, and muscle (e.g. pain, weakness, fatiguability), calling to mind classical so-called mitochondrial “encephalomyopathy”. The brain and muscle are highly energy demanding “aerobic” postmitotic tissues, so are especially vulnerable. In both settings, there are high rates of GI and neurological symptoms, recalling mitochondrial neurogastroencephalomyopathy. Sleep, neurological, psychiatric, dermatologic, shortness of breath, are also common in both. Finally, in both, a range of additional problems are observed in smaller subsets, spanning virtually every organ system (since cell energy is required for every function in the body)
d. There is variable latency to onset of symptoms (that again vary from person to person), as is classical in mitochondrial disease. Symptoms continued to emerge at elevated rates after servicepersons were no longer deployed in the Gulf. This is consistent with mitochondrial phenomena termed “heteroplasmy” and “threshold effects”. (Baseline vulnerability of an organ depends on that organ’s cells balance of mitochondrial mutations, which aren’t the same from organ to organ; and damage can lead to more damage as impaired mitochondria produce oxidative stress, which yields symptoms when a threshold is surpassed, of either cell death or amount of mitochondrial dysfunction — so-called threshold effects.)
III. The profile of other conditions, and of objective markers shown to be altered, are also compatible with mitochondrial disease.
For instance:
a. Routine blood tests are commonly normal.
b. Gulf War veterans showed elevated rates of ALS in three separate studies. ALS is condition tied to mitochondrial dysfunction in a vicious cycle with oxidative stress
c. Other objective markers that are abnormal in Gulf War illness and Gulf War veterans – increased autonomic dysfunction, increased coagulation activation, increased autoimmune markers, etc — are each expected sequelae of intertwined mitochondrial dysfunction and oxidative stress.
a. Routine blood tests are commonly normal.
b. Gulf War veterans showed elevated rates of ALS in three separate studies. ALS is condition tied to mitochondrial dysfunction in a vicious cycle with oxidative stress
c. Other objective markers that are abnormal in Gulf War illness and Gulf War veterans – increased autonomic dysfunction, increased coagulation activation, increased autoimmune markers, etc — are each expected sequelae of intertwined mitochondrial dysfunction and oxidative stress.
Clinicians should also take from this report that these veterans’ suffering is real and due to “organic” causes, not in any way “all in their heads.”
It is a tragedy that cannot be undone that many affected veterans attest they have been subjected to derision rather than compassion, and dismissiveness rather than help. But perhaps armed with better information, physicians may do better in the future.
It is a tragedy that cannot be undone that many affected veterans attest they have been subjected to derision rather than compassion, and dismissiveness rather than help. But perhaps armed with better information, physicians may do better in the future.
Also, these findings suggest that treatment approaches targeting bioenergetics and oxidative stress (and downstream sequelae of these) may confer benefit to those who are affected.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Golomb: Replication is always desirable, and is currently planned..
A randomized trial of coenzyme Q10 (vs placebo) should be published this year.
A randomized trial of coenzyme Q10 (vs placebo) should be published this year.
More research will be needed to continue to understand the secondary mechanisms involved; and to identify and test promising treatments to mitigate the ongoing suffering and impaired function of these veterans.
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