Research shows how a diet change might help US veterans with Gulf War illness
August 31, 2020
Science Daily/American University
A new study from American University shows the results from a dietary intervention in U.S. veterans suffering from Gulf War Illness, a neurological disorder in veterans who served in the Persian Gulf War from 1990 to 1991.
The veterans' overall number of symptoms were reduced and they experienced less pain and fatigue after one month on a diet low in glutamate, which is a flavor enhancer commonly added to foods, and that also functions as an important neurotransmitter in the nervous system.
Because the symptoms of GWI are similar to those of fibromyalgia, the U.S. Department of Defense provides funding for previously tested treatments in fibromyalgia that could also help veterans suffering from GWI. The low glutamate diet was previously shown to reduce symptoms in fibromyalgia, and thus, was a candidate for this funding. There are no cures for either illness, and treatments are being sought for both to manage chronic pain. GWI is thought to be connected to nervous system dysfunction in veterans. In the Gulf War, soldiers were exposed to various neurotoxins such as chemical warfare agents, pyridostigmine bromide (PB) pills, pesticides, burning oil fields, and depleted uranium.
"Gulf War Illness is a debilitating disorder which includes widespread pain, fatigue, headaches, cognitive dysfunction, and gastrointestinal symptoms. Veterans with GWI have a reduced quality of life as compared to veterans who do not have the illness," said AU Associate Professor of Health Studies Kathleen Holton, who explores how food additives contribute to neurological symptoms and is a member of AU's Center for Behavioral Neuroscience. "In this study testing the low glutamate diet, the majority of veterans reported feeling better. We saw significant reductions in their overall number of symptoms and significant improvements in pain and fatigue."
The study, published in the journal Nutrients, details the experiments in a clinical trial of 40 veterans with GWI. The study participants were randomized to either immediately start the low glutamate diet for one month, or to a control group. After completion of the one-month diet, participants were challenged with monosodium glutamate and placebo to see if symptoms returned.
The challenge with MSG versus placebo resulted in significant variability in response among participants, with some subjects worsening, while others actually improved. This suggests that while a diet low in glutamate can effectively reduce overall symptoms, pain, and fatigue in GWI, more research is needed to understand how the diet may be altering how glutamate is handled in the body, and the specific role that nutrients may play in these improvements.
The role of glutamate
Glutamate is most easily identified when it is in the form of the food additive MSG; however, it appears most commonly in American diets hidden under many other food additive names in processed foods. Americans also consume glutamate through some foods where it occurs naturally, such as soy sauce, fish sauce, aged cheeses like parmesan, seaweed, and mushrooms.
Glutamate is known to play a role in pain transmission, where it functions as an excitatory neurotransmitter in the nervous system. When there's too much of it, it can cause disrupted signaling or kill cells, in a process called excitotoxicity. Previous research has shown that glutamate is high in pain processing areas of the brain in individuals with fibromyalgia and migraine. High concentrations of glutamate have also been linked to epilepsy, multiple sclerosis, Parkinson's disease, ALS, cognitive dysfunction (including Alzheimer's), and psychiatric issues such as depression, anxiety and PTSD.
In her research, Holton limits people's exposure to glutamate, while also increasing intake of nutrients known to protect against excitotoxicity. She analyzes how diet affects cognitive function, brain wave activity, brain glutamate levels, and brain function using MRI. In the study of veterans, the low glutamate diet was made up of whole foods low in additives and high in nutrients. Holton theorizes that the increased consumption of nutrients that are protective against excitotoxicity may have led to improved handling of glutamate in the nervous system. The study and diet tested in the veterans were similar to her previous studies, where she observed improvements in those with fibromyalgia, as well as in Kenyan villagers living with chronic pain.
It will take more research to determine if reducing exposure to glutamate can be used as a treatment for chronic widespread pain and other neurological symptoms in U.S. veterans with GWI. Holton is currently pursuing funding for her next grant, which will recruit 120 veterans for a Phase 3 clinical trial to confirm the study's findings in a larger group, and further explore the mechanisms for these effects.
https://www.sciencedaily.com/releases/2020/08/200831112333.htm
Female Gulf War combat veterans have persistent symptoms more than 25 years later
May 26, 2020
Science Daily/Medical College of Georgia at Augusta University
More than a quarter century after the Gulf War, female veterans who saw combat have nearly a twofold risk of reporting more than 20 total medical symptoms, like cognition and respiratory troubles, than their fellow female veterans who were not deployed, investigators report.
A sizeable percentage of the female combat veterans still report neurological symptoms; about two-thirds report difficulty remembering new information and trouble concentrating, investigators report in the Journal of Women's Health.
An association with more headaches among the combat veterans also was reported and there were "strong associations" between deployment status and respiratory symptoms with 39% of combat veterans still reporting difficulty breathing or shortness of breath. More than half also report a low tolerance for heat and cold.
"It's been over 25 years since the war ended and these are very persistent health outcomes," says Dr. Steven S. Coughlin, interim chief of the Division of Epidemiology in the Medical College of Georgia Department of Population Health Sciences. "This tells us that the way the Gulf War illness manifests itself may be different in female than male veterans, so it's important to take gender into account," says Coughlin.
Twenty years ago, female Gulf War veterans were reporting similar problems, investigators say. The newly reported findings indicate the women are showing increased frequency of symptoms over time and above the rate that would be expected with normal aging, the investigators say. Their reported symptoms correspond with higher rates of diabetes, osteoporosis, thyroid problems, asthma and irritable bowel syndrome in this and similar groups.
Additional studies are needed to find biomarkers of Gulf War illness in these former soldiers and effective treatments, they write.
"We think this has a lot of importance for the health of these veterans and hopefully, when combined with information from other studies, it will lead to improved treatment," Coughlin says.
Three hundred-and-one female Gulf War veterans from all military branches participated in the study, including 203 who were deployed and 98 who were not sent directly into a war zone.
Other persistent problems war zone veterans report include about a third saying they frequently cough when they do not have a cold. Many of their reported symptoms fit the definition of Gulf War illness, which includes having at least three of six symptom categories that include fatigue, neurological/cognitive/mood problems, pain as well as respiratory, gastrointestinal and skin problems. Younger, non-white, female Army veterans were likely to report the most symptoms, they say.
Their significant symptom burden would likely impact the veterans' quality of life and require medical evaluation and treatment, Coughlin and his colleagues write.
"We are trying to fill in this gap in the published literature about Gulf War illness among women veterans because they have been greatly understudied," Coughlin says, referencing the first conflict in which the United States included a sizeable female contingent directly in warfare.
The gender differences they are finding are consistent with earlier studies as well as other current ones coming out of Florida-based Nova Southeastern University, for example, where they are conducting a clinical trial to try to reverse some of the ill effects, he says.
The findings also are more evidence that the female veterans of the Gulf War may have more chronic health issues and conditions than other groups of women generally or female veterans specifically.
Coughlin theorizes that females may be more susceptible to some of the wartime hazards because on average their body size is smaller and because of other differences in physiology. "We can only speculate," he adds.
When troops started to come home from the Middle East following the conflict that lasted from August 1990 through February 1991, they reported a constellation of symptoms, including headaches, gastrointestinal complaints, skin ailments, forgetfulness, fatigue, particularly after exertion, and musculoskeletal pain, says Coughlin, who served as a senior epidemiologist with the Department of Veterans Affairs Central Office in Washington, D.C. The leading theory early on was that it was a psychogenic illness, somewhat similar to the PTSD experienced by many Vietnam War veterans. Now the consensus is that much of it results from the neurological impact of neurotoxins soldiers on the frontline were exposed to, Coughlin says.
"They were inundated with pesticides, there are a lot of biting flies and pests in that part of the world so they had uniforms infused with pesticides, a lot of them even wore a dog's flea collar for extra protection," he says. Soldiers also were asked to take pyridostigmine bromide, a drug given to patients with myasthenia gravis to improve muscle strength, prophylactically to help protect them from nerve agents in field, but the drug itself is mildly toxic to nerves and there is some evidence that, in combination with some of the insecticides used, it becomes more potent.
"Every time the alarms went off, they would have to take these little white pills," Coughlin says. There were other environmental toxins as well, like blown up munitions factories and low dose exposure to sarin nerve gas and others. "It's similar to what you see among agricultural workers exposed to pesticides," he notes. The veterans also were exposed to hazards such as smoke from oil well fires and burn pits used to incinerate waste, the investigators write.
The new study looked at the frequency and patterns of health symptoms in the female veterans as well as military service and lifestyle. The investigators theorized that symptoms associated with Gulf War illness would be more prominent in the women who saw conflict.
They found the deployed veterans were significantly more likely to report seven symptoms consistent with Gulf War illness, including low tolerance for heat or cold, difficulty breathing or shortness of breath, frequent coughing without having a cold, difficulty concentrating and remembering recent information, feeling down or depressed and anxious, the investigators write. Those deployed were more than twice as likely to report more total symptoms and nonwhites -- including American Indians, Alaska natives as well as Asian Americans and Pacific Islands Americans -- were four times more likely to report symptoms than whites. Older women were less likely than younger women to report symptoms and those enlisted in the Air Force and Navy were significantly less likely to report more symptoms than those in the Army.
Participants in the study were a mean age of early 50s and other demographics, like race, ethnicity and education, were similar, but those who saw combat were more likely to have served in the Army or Navy and less likely to have served in the Air Force.
They were taken from a national cohort of 1,318 Gulf War veterans created from the Veterans Affairs Cooperative Studies Program 585 Gulf War Era Cohort and Biorepository pilot study. Outcomes of female veterans in the group have not been reported separately. Women comprised 7% of the 700,000 military personnel to serve in the Gulf War, the largest number of women to serve in a war zone in U.S. military history at that time. The influx of the some 50,000 female Gulf War veterans resulted in the establishment of specialty clinics for them at VA hospitals. Evidence indicates about 19% of women veterans still have delayed or unmet health care needs, possibly because of expanded military roles for women, including increased exposure to combat, the investigators write.
Female veterans who have been involved in conflicts since the Vietnam War report higher rates of poor sleep quality, fatigue, insomnia, chronic pain, including headache and musculoskeletal complaints, respiratory problems and skin problems, as well as cognitive and mood related complaints, Coughlin and his colleagues write.
https://www.sciencedaily.com/releases/2020/05/200526091406.htm
Can light therapy help the brain?
April 2, 2015
Veterans Affairs Research Communications
An innovative therapy that applies red and near-infrared light to the brain is now being tested for Gulf War Illness, traumatic brain injury, and PTSD.
Following up on promising results from pilot work, researchers at the VA Boston Healthcare System are testing the effects of light therapy on brain function in veterans with Gulf War Illness.
Veterans in the study wear a helmet lined with light-emitting diodes that apply red and near-infrared light to the scalp. They also have diodes placed in their nostrils, to deliver photons to the deeper parts of the brain.
The light is painless and generates no heat. A treatment takes about 30 minutes.
The therapy, though still considered "investigational" and not covered by most health insurance plans, is already used by some alternative medicine practitioners to treat wounds and pain. The light from the diodes has been shown to boost the output of nitric oxide near where the LEDs are placed, which improves blood flow in that location.
"We are applying a technology that's been around for a while," says lead investigator Dr. Margaret Naeser, "but it's always been used on the body, for wound healing and to treat muscle aches and pains, and joint problems. We're starting to use it on the brain."
Naeser is a research linguist and speech pathologist for the Boston VA, and a research professor of neurology at Boston University School of Medicine (BUSM). She is also a licensed acupuncturist and has conducted past research on laser acupuncture to treat paralysis in stroke, and pain in carpal tunnel syndrome.
The LED therapy increases blood flow in the brain, as shown on MRI scans. It also appears to have an effect on damaged brain cells, specifically on their mitochondria. These are bean-shaped subunits within the cell that put out energy in the form of a chemical known as ATP. The red and near-infrared light photons penetrate through the skull and into brain cells and spur the mitochondria to produce more ATP. That can mean clearer, sharper thinking, says Naeser.
Naeser says brain damage caused by explosions, or exposure to pesticides or other neurotoxins--such as in the Gulf War--could impair the mitochondria in cells. She believes light therapy can be a valuable adjunct to standard cognitive rehabilitation, which typically involves "exercising" the brain in various ways to take advantage of brain plasticity and forge new neural networks.
"The light-emitting diodes add something beyond what's currently available with cognitive rehabilitation therapy," says Naeser. "That's a very important therapy, but patients can go only so far with it. And in fact, most of the traumatic brain injury and PTSD cases that we've helped so far with LEDs on the head have been through cognitive rehabilitation therapy. These people still showed additional progress after the LED treatments. It's likely a combination of both methods would produce the best results."
The LED approach has its skeptics, but Naeser's group has already published some encouraging results in the peer-reviewed scientific literature.
Last June in the Journal of Neurotrauma, they reported the outcomes of LED therapy in 11 patients with chronic TBI, ranging in age from 26 to 62. Most of the injuries occurred in car accidents or on the athletic field. One was a battlefield injury, from an improvised explosive device (IED).
Neuropsychological testing before the therapy and at several points thereafter showed gains in areas such as executive function, verbal learning, and memory. The study volunteers also reported better sleep and fewer PTSD symptoms.
The study authors concluded that the pilot results warranted a randomized, placebo-controlled trial--the gold standard in medical research.
That's happening now, thanks to VA support. One trial, already underway, aims to enroll 160 Gulf War veterans. Half the veterans will get the real LED therapy for 15 sessions, while the others will get a mock version, using sham lights.
Then the groups will switch, so all the volunteers will end up getting the real therapy, although they won't know at which point they received it. After each veteran's last real or sham treatment, he or she will undergo tests of brain function.
Naeser points out that "because this is a blinded, controlled study, neither the participant nor the assistant applying the LED helmet and the intranasal diodes is aware whether the LEDs are real or sham. So they both wear goggles that block out the red LED light." The near-infrared light is invisible to begin with.
Besides the Gulf War study, other trials of the LED therapy are getting underway:
· Later this year, a trial will launch for veterans age 18 to 55 who have both traumatic brain injury (TBI) and posttraumatic stress disorder--a common combination in recent war veterans. The VA-funded study will be led by Naeser's colleague Dr. Jeffrey Knight, a psychologist with VA's National Center for PTSD and an assistant professor of psychiatry at BUSM.
· Dr. Yelena Bogdanova, a clinical psychologist with VA and assistant professor of psychiatry at BUSM, will lead a VA-funded trial looking at the impact of LED therapy on sleep and cognition in veterans with blast TBI.
· Naeser is collaborating on an Army study testing LED therapy, delivered via the helmets and the nose diodes, for active-duty soldiers with blast TBI. The study, funded by the Army's Advanced Medical Technology Initiative, will also test the feasibility and effectiveness of using only the nasal LED devices--and not the helmets--as an at-home, self-administered treatment. The study leader is Dr. Carole Palumbo, an investigator with VA and the Army Research Institute of Environmental Medicine, and an associate professor of neurology at BUSM.
Naeser hopes the work will validate LED therapy as a viable treatment for veterans and others with brain difficulties. She foresees potential not only for war injuries but for conditions such as depression, stroke, dementia, and even autism.
"There are going to be many applications, I think. We're just in the beginning stages right now."
http://www.sciencedaily.com/releases/2015/04/150402161648.htm