# Mechanisms of Gulf War Illness

> **NIH VA I01** · MEMPHIS VA MEDICAL CENTER · 2024 · —

## Abstract

Since 2001, more than 2.2 million US veterans have served in Operation Enduring Freedom (OEF)
in Afghanistan and Operation Iraqi Freedom (OIF) in Iraq. The Gulf Registry of the VA Environmental
Epidemiology Service identified the majority of these veterans as having chronic health complaints of
undetermined etiology. Among the symptoms most frequently reported by veterans with Gulf War
Illness (GWI) were chronic fatigue, frequent or persistent headache, frequent or persistent muscle or
joint pain, and gastrointestinal (GI) symptoms. GI symptoms (e.g., diarrhea, bloating, and abdominal
pain) reported by these veterans accounted for most complaints. Indeed, up to 33% of veterans with
GWI suffer from chronic GI symptoms.
 We have shown that veterans with GWI and GI symptoms have increased intestinal permeability
that drives GI symptoms (Zhang et al., 2019). Our research group recently completed a clinical trial
demonstrating the effectiveness of oral glutamine supplementation in diarrhea-predominant IBS
patients with increased intestinal permeability (Zhou et al., 2019). We now have obtained preliminary
evidence that oral glutamine supplementation may restore intestinal permeability in veterans with GWI
and GI symptoms. Based on these new findings, we hypothesize that oral glutamine supplementation
will improve the Symptom Severity Scale and restore intestinal permeability in veterans with GWI and
chronic GI symptoms. We propose to conduct a randomized, double-blind, placebo-controlled clinical
trial studying oral glutamine supplementation compared to placebo in veterans with GWI and GI
symptoms.
 The human GI tract is the major site of glutamine utilization in the body. Glutamine is a major
energy source for rapidly dividing intestinal mucosal cells of the digestive tract. Glutamine helps to
protect the lining of the GI tract. Its depletion results in epithelial atrophy and a subsequent increase in
intestinal permeability. Glutamine supplementation has been shown to decrease bacterial translocation
and intestinal permeability after intestinal injury. Glutamine supplementation has also been shown to
decrease intestinal permeability and improve GI function in patients with Crohn’s disease, advanced
esophageal cancer, or metastatic cancer undergoing radio chemotherapy. There are no published
studies to date to support the use of glutamine for veterans with GWI and chronic GI symptoms.
However, given our published studies, preliminary data demonstrating restoration of intestinal
permeability with oral glutamine therapy, and the mechanisms of action of glutamine on the GI tract,
research testing whether oral glutamine is an effective therapy in veterans with GWI is needed. Given
that there are no effective treatments for these veterans and that current treatment approaches are far
from ideal, this proposed clinical trial would be extremely important as it would not only have a
beneficial impact on the health of many of our veterans, but also it would su...

## Key facts

- **NIH application ID:** 10702046
- **Project number:** 2I01CX001477-06A1
- **Recipient organization:** MEMPHIS VA MEDICAL CENTER
- **Principal Investigator:** George Nicholas Verne
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2017-04-01 → 2027-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10702046

## Citation

> US National Institutes of Health, RePORTER application 10702046, Mechanisms of Gulf War Illness (2I01CX001477-06A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10702046. Licensed CC0.

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