The Low Glutamate Diet Effectively Improves Pain and Other Symptoms of Gulf War Illness, 2020, Baraniuk

Tom Kindlon · Sep 1, 2020

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The Low Glutamate Diet Effectively Improves Pain and Other Symptoms of Gulf War Illness
Kathleen F. Holton 1,2,* , Anna E. Kirkland 3, Michael Baron 4, Shalini S. Ramachandra 1,
Mackenzie T. Langan 5 , Elizabeth T. Brandley 1 and James N. Baraniuk 6

1
Department of Health Studies, American University, Washington, DC 20016, USA
2
Center for Behavioral Neuroscience, American University, Washington, DC 20016, USA
3
Program in Behavior, Cognition and Neuroscience, American University, Washington, DC 20016, USA
4
Department of Mathematics & Statistics, American University, Washington, DC 20016, USA
5
Neuroscience Program, Department of Biology, American University, Washington, DC 20016, USA
6
Department of Medicine, Georgetown University, Washington, DC 20057, USA
*

Nutrients 2020, 12(9), 2593; https://doi.org/10.3390/nu12092593
Received: 30 June 2020 / Revised: 17 August 2020 / Accepted: 20 August 2020 / Published: 26 August 2020
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Abstract

Gulf War Illness (GWI) is a multisymptom disorder including widespread chronic pain, fatigue and gastrointestinal problems.

The objective of this study was to examine the low glutamate diet as a treatment for GWI.

Forty veterans with GWI were recruited from across the US.

Outcomes included symptom score, myalgic score, tender point count, dolorimetry and the Chalder Fatigue Scale.

Subjects were randomized to the low glutamate diet or a wait-listed control group, with symptom score being compared after one month.

Subjects then went onto a double-blind, placebo-controlled crossover challenge with monosodium glutamate (MSG)/placebo to test for return of symptoms.

Symptom score was compared between diet intervention and wait-listed controls with an independent t-test and effect size was calculated with Cohen’s d.

Change scores were analyzed with Wilcoxon Signed Rank tests.

Crossover challenge results were analyzed with General Linear Models and cluster analysis.

The diet intervention group reported significantly less symptoms (p = 0.0009) than wait-listed controls, with a very large effect size, d = 1.16.

Significant improvements in average dolorimetry (p = 0.0006), symptom score, tender point number, myalgic score and the Chalder Fatigue Scale (all p < 0.0001) were observed after the 1-month diet.

Challenge with MSG/placebo resulted in significant variability in individual response.

These results suggest that the low glutamate diet can effectively reduce overall symptoms, pain and fatigue in GWI, but differential results upon challenge suggest that other aspects of the diet, or underlying differences within the population, may be driving these changes.

Future research is needed to identify potential nutrient effects, biomarkers, and underlying metabolic differences between responders and non-responders.

Keywords: Gulf War Illness; GWI; glutamate; diet; pain; fatigue; symptoms; treatment
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Tom Kindlon · Sep 1, 2020

Twenty-eight of 39 participants satisfied CFS criteria.

One ME/CFS patient discussed this type of diet in a series of tweets here:
https://twitter.com/McDrowsy/status/1300580708486770688

Andy · Sep 1, 2020

Any objective measures?

Midnattsol · Sep 1, 2020

Hasn't this been discussed in another thread? Or was that a low glutamate diet for fibromyalgia? Anyhow, if their "low glutamate diet" is like the other low glutamate diet and actually a "low preprocessed food with added MSG diet" it's misleading. Glutamate levels can be affected by other things, perhaps by increasing vegetable intake..

Midnattsol · Sep 1, 2020

Tom Kindlon said: ↑

Twenty-eight of 39 participants satisfied CFS criteria.

One ME/CFS patient discussed this type of diet in a series of tweets here:
https://twitter.com/McDrowsy/status/1300580708486770688
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But the question is - do you have to remove food that naturally contains glutamate? Some of the foods listed in this thread are associated with inflammation for other reasons than their glutamate content (I get symptoms if I eat nightshades). Other dietary approaches that change your metabolism could work the same way, by regulating glutamate:glutamine ratio, I'd think of typical "anti inflammatory diets" (of which many include tomatoes, not everyone are as sensitive to nightshades as I am).

Hutan · Sep 1, 2020

Nerve agents, PB pills and pesticides are all acetylcholinesterase (AChE) inhibitors. When AChE is inhibited, it prevents the breakdown of acetylcholine (ACh) in the synapse which leads to the overactivation of the ACh receptors, and can result in deleterious effects ranging from increased neuronal hyper-excitability to death from seizures or respiratory paralysis [7,8]. However, ACh dysregulation alone does not account for symptoms of GWI [9]. ACh dysregulation has downstream effects on glutamate (Glu), the most ubiquitous excitatory neurotransmitter in the CNS, which results in glutamatergic excitotoxicity, mainly through the overactivation of the N-methyl-D-aspartate (NMDA) ionotropic glutamate receptor [10]. Glutamatergic excitotoxicity triggers neuroinflammation and oxidative stress contributing to increased blood–brain barrier (BBB) permeability and neuronal cell death [8]. The cascade of CNS dysfunction from neurotoxic exposures mediated by glutamatergic excitotoxicity has been proposed as a potential mechanism for GWI and is reviewed in detail elsewhere
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Glutamate receptors are found throughout the central and peripheral nervous systems, on immune cells, and on many organs (e.g., pancreas, heart, kidney, lungs, skin, gastrointestinal tract) [16]. Therefore, the wide-ranging location of glutamate receptors may contribute to the diverse symptom presentation within GWI. Furthermore, glutamate mediated central sensitization is associated with multisymptom illnesses, which include symptoms such as migraine, cognitive dysfunction, chronic fatigue, and even gastrointestinal issues [17]. Together, it seems as though glutamate dysregulation may be a vital component of GWI.
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The idea of acetylcholinesterase inhibitors interests me because I and my two children were exposed to methyl bromide and its downstream products immediately before becoming ill with ME/CFS. The authors have this idea that acetylcholine dysregulation makes glutamate receptors over-activated and this causes neuroinflammation and a permeable blood-brain barrier. I am not understanding how that can cause a chronic but fluctuating outcome.

But assuming all that is true, does reducing glutamate in the diet help people with Gulf War illness?

40 GWI people - 20 allocated to a low glutamate diet, 20 on wait list (who subsequently also had a go with the diet). So, an open label trial. The diet was a healthy diet with added micronutrients, possibly much better than some of the participants' usual diets. All outcomes were subjective.

65% of participants were considered improved when using the criteria of ≥30% of symptoms remitting after one-month on the diet. ....Similarly, those with chronic fatigue syndrome were marginally less likely to report this level of symptom remission.
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Here's an example of the reported change in symptoms:

I think that level of change is easily explained by the placebo effect of an open-label trial, perhaps assisted by a better diet for some of the participants.

I haven't looked into the stats of the MSG challenges after the one month trial but it sounds like things were all over the place.

Challenge with MSG/placebo resulted in significant variability in individual response.
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I end up being annoyed. Why did they not do a proper blinded trial with everyone on a low MSG diet and some people taking MSG capsules? This study tells us nothing, other than a low-glutamate diet does not cure people with GWI.

To our knowledge, this is the first study to result in widespread symptom improvement in Gulf War Illness and no study has come close to the very large effect size observed herein. Furthermore, there were zero side effects to this intervention, making it a safer alternative to the many drug options currently being used.
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Despite a trial design and outcome that do not provide any evidence that a low glutamate diet helps, the authors seem to be talking up the trial as a great success.

Midnattsol · Sep 1, 2020

Hutan said: ↑

The idea of acetylcholinesterase inhibitors interests me because I and my two children were exposed to methyl bromide and its downstream products immediately before becoming ill with ME/CFS. The authors have this idea that acetylcholine dysregulation makes glutamate receptors over-activated and this causes neuroinflammation and a permeable blood-brain barrier. I am not understanding how that can cause a chronic but fluctuating outcome.

But assuming all that is true, does reducing glutamate in the diet help people with Gulf War illness?

40 GWI people - 20 allocated to a low glutamate diet, 20 on wait list (who subsequently also had a go with the diet). So, an open label trial. The diet was a healthy diet with added micronutrients, possibly much better than some of the participants' usual diets. All outcomes were subjective.

Here's an example of the reported change in symptoms:
View attachment 11905
I think that level of change is easily explained by the placebo effect of an open-label trial, perhaps assisted by a better diet for some of the participants.

I haven't looked into the stats of the MSG challenges after the one month trial but it sounds like things were all over the place.

I end up being annoyed. Why did they not do a proper blinded trial with everyone on a low MSG diet and some people taking MSG capsules? This study tells us nothing, other than a low-glutamate diet does not cure people with GWI.

Despite a trial design and outcome that do not provide any evidence that a low glutamate helps, the authors seem to be talking up the trial as a great success.
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Welcome to the world of nutritional science

Re fluctuating symptoms - you can have fluctuating levels of the metabolites that are causing problems I guess.

shak8 · Sep 1, 2020

Small study (N=40).

Great results when following low glutamate diet ('following' is a bit sketchy as are most dietary studies).

These results are subjective for the most part.

Also, the least improvement was for joint and muscle pain.

But when the double-crossover groups were challenged with MSG capsules, there was no clear evidence of worsening symptoms.

And were the results (especially the gastrointestinal symptoms) the result of more fiber in their diets or the result of some other nutrients, other than glutamate?

The body and brain have their own tricky way of balancing out dietary glutamates, I think.

Edited to add: How can this study be termed 'double-blind' when half the participants are knowingly following the strict diet (they are not blinded). There's an obvious built-in placebo response here. The other arm is the waiting list, or diet as usual--no change would be expected anyway.

Another personal quip in medical research: when a one-trick pony (a pill, a chemical) is proposed for what ails one, I get suspicious.

wastwater · Sep 3, 2020

https://www.verywellhealth.com/what-is-glutamate-715862
CFS & FIBROMYALGIA
What is Glutamate?

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