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

Pilot study in Kenya shows link between chronic pain and glutamate consumption

Researchers test theory that diet change can alleviate pain

February 16, 2018

Science Daily/American University

Preliminary research from a small pilot study carried out in Meru, in eastern Kenya, shows a link between chronic pain and consumption of glutamate, a common flavor enhancer found in Western and non-Western diets worldwide.

Chronic pain is among the most vexing health problems, including in the developing world, where most research suggests that the prevalence of pain is similar to the United States and other developed nations.

Preliminary research from a small pilot study carried out in Meru, in eastern Kenya, shows a link between chronic pain and consumption of glutamate, a common flavor enhancer found in Western and non-Western diets worldwide. Results demonstrated that when study participants cut monosodium glutamate from their diets, their symptoms improved. The findings are published in the journal Nutrition.

"This preliminary research in Kenya is consistent with what I am observing in my chronic pain research here in the United States," said Kathleen Holton, lead author of the study and assistant professor of health studies at American University. "We don't know what exposure is leading to this susceptibility to dietary glutamate, but this pilot study suggests the need for a large-scale clinical trial, since dietary change could be an effective low-cost treatment option for developing countries."

As researchers study glutamate, they're gaining insights into how the chemical works in the human brain and body. In the brain, glutamate is a common neurotransmitter. It also can act as an excitotoxin, over-stimulating and damaging or killing nerve cells. Some research has found that increased consumption of glutamate may enhance chronic pain symptoms, so there is biological cause for scientists to examine the chemical in relation to pain.

Glutamate is also a naturally occurring chemical in some foods, like soy sauce and parmesan cheese, but is more commonly found as a food additive. In the U.S., glutamate is added to many food products and found under many names including 'monosodium glutamate,' 'hydrolyzed protein,' 'protein isolate,' 'protein extract' and 'autolyzed yeast extract,' just to name a few. In Kenya, people's exposure to glutamate is only from a few foods which contain MSG, with the largest exposure being from a mixed seasoning spice called Mchuzi Mix, which is typically used in cooking daily.

In the Kenya study, the goal was to test whether a dietary intervention could perform as well as or better than over-the-counter medication in relieving pain. With a sample size of 30 participants, the researchers tested the effects of removing MSG, increasing water intake, or a combination of both, relative to acetaminophen (the main treatment option available in Meru). Study participants experienced chronic pain for at least three months or more and in at least three quadrants of the body. Similar to what is seen with widespread chronic pain patients in the U.S., most also suffered from other neurological symptoms, including headaches or migraines, chronic fatigue, cognitive dysfunction, and sleep issues.

Holton's collaborators in the research were University of Michigan Professor Dr. Daniel J. Clauw, M.D., and Dr. Peter K. Ndege, M.D., of Meru University of Science and Technology in Kenya. This research came about after Clauw learned about Meru villagers' plight with chronic pain. When the team initially surveyed residents in the area, an estimated 60 percent reported chronic pain, twice the amount typically observed.

The participants were broken into four groups. Because dehydration is associated with headache pain, the researchers factored that into the study design. The groups consisted of the following: If subjects commonly consumed Mchuzi Mix, they were given a similar mixed seasoning substitute that contained no MSG. Those reporting low water intake and no MSG were given bottled water and instructed to increase water consumption to eight cups a day.

Those with low water consumption who also consumed MSG were given water and the substitute spices. The control group had neither exposure and was given acetaminophen. The group that removed MSG from its diet and consumed more water reported significant improvements in their symptoms, as did the group receiving acetaminophen.

In the future, Holton, Clauw and Ndege plan a larger, epidemiological survey to further understand the prevalence of widespread chronic pain in the region and to train Kenyan research staff how to conduct a large-scale clinical trial to test if dietary change could be an effective, low-cost treatment option for pain in countries like Kenya.

"This would be incredible if we could impact chronic pain simply by making slight modifications to diet," said Clauw, a leading expert on chronic pain.

https://www.sciencedaily.com/releases/2018/02/180216142702.htm