Office of Research & Development
VA Research is conducting studies to better understand and treat the health problems experienced by some Veterans of the 1990-1991 Gulf War.
Nearly 700,000 men and women served in the Persian Gulf during operations Desert Shield and Desert Storm in the early 1990s. A 2016 epidemiological study by VA Office of Public Health researchers, based on data that were collected in 2012, indicated that almost 20 years after the Gulf War, Veterans of that war continue to report poorer health than those who served at the same time but did not see service in the gulf.
A prominent condition affecting Gulf War Veterans is a cluster of medically unexplained chronic symptoms that can include fatigue, headaches, joint pain, indigestion, insomnia, dizziness, respiratory disorders, skin problems, and memory impairment. VA refers to these illnesses as "chronic multisymptom illness" (CMI) and "undiagnosed illnesses."
Because the symptoms vary widely, VA prefers not to use the term "Gulf War Syndrome" when referring to medically unexplained symptoms reported by Gulf War Veterans. However, the condition is often referred to as "Gulf War illness" by VA clinicians and researchers and in the medical literature.
The 2016 epidemiological study referenced above found that at as many as 300,000 Veterans, nearly 44 percent—about 4 in 10 of those who deployed to the Persian Gulf during Desert Shield and Desert Storm—are now estimated to have Gulf War Illness, based on the latest data.
VA has also determined that nine infectious diseases are related to military service in the first Gulf War, Iraq, and Afghanistan. They include malaria, brucellosis, campylobacter jejuni, coxiella burnetli (Q fever), mycobacterium tuberculosis, nontyphoid salmonella, shigella, visceral leishmaniasis, and west Nile virus. A fuller description of these diseases can be found here.
VA's Gulf War registry health exam alerts Veterans to possible long-term health problems that may be related to environmental exposures during their military service. The registry data helps VA understand and respond to these health problems more effectively.
The comprehensive health exam includes an exposure and medical history, laboratory tests, and a physical exam. A VA health professional discusses the results face-to-face with the Veteran and in a follow-up letter.
All Veterans who served in the Gulf during Operation Desert Shield, Operation Desert Storm, Operation Iraqi Freedom, or Operation New Dawn are eligible for the exam, which is separate from VA's disability compensation process. Veterans do not need to be enrolled in VA health care to take part.
For more information on VA's efforts on behalf of Gulf War Veterans, particularly in the areas of epidemiology and surveillance, visit the Gulf War Veterans' Illnesses section of the VA Office of Public Health website.
VA researchers are learning about conditions affecting Gulf War Veterans and identifying the best ways to diagnose and treat them. Their efforts are guided by a strategic plan for Gulf War research developed with input from leading scientists and researchers, physicians, and Veterans themselves.
The plan was developed in 2012 in response to a call from the Institute of Medicine (now the National Academy of Medicine) for a renewed and better-focused effort in the area of Gulf War research. It comprehensively addresses a range of issues related to Gulf War research and strongly emphasizes the need for effective treatment for the symptoms Veterans experience.
Along with the specific research areas outlined in the strategic plan, VA investigators are conducting research in many other areas important to Gulf War Veterans. These include studies on pain, autoimmune disease, neurodegenerative disease, sleep disorders, gastrointestinal disorders, respiratory problems, and other chronic diseases.
The Research Advisory Committee on Gulf War Veterans' Illnesses makes recommendations to the Secretary of Veterans Affairs on government research relating to the health consequences of military service in the Southwest Asia theater of operations during the Persian Gulf War.
The Committee is charged with reviewing previous medical research and other relevant medical knowledge, and making recommendations for future research. It was created by Congress in 1998. The guiding principle for the work of the Committee is the premise that the fundamental goal of Gulf War-related government research is to improve the health of Gulf War Veterans.
One of the largest studies on the health of Gulf War Veterans is VA's Longitudinal Health Study of Gulf War Era Veterans. This study, conducted by VA's Office of Public Health, compares changes in health status over time between deployed and non-deployed Veterans from the Gulf War era. Approximately 30,000 Veterans are taking part in the study.
The study group includes Veterans who served in different branches of service, representing active duty, reservists, and National Guard members. A special effort was made to ensure women are appropriately represented (women constitute 20 percent of the sample).
The study team's initial report was published in 2000. It concluded that in comparison with their peers, Gulf veterans had a higher prevalence of functional impairment, health care utilization, symptoms, and medical conditions. They also rated their overall health status, including their mental, physical, and social wellbeing, less highly than their fellow Veterans who did not serve in the Gulf.
Results of a follow-up survey were published in 2011. At that time, researchers found that deployed Veterans of the Gulf War era were more likely to report new health problems, and their existing illnesses were more likely to linger.
In 2016, VA published the results of a second follow-up study, using data collected in 2012 and 2013. This study found that almost 20 years after the Gulf War, Veterans of the war continued to report poorer health than Gulf-era Veterans.
Although the prevalence of self-reported health conditions and positive screens of mental health conditions are higher in Gulf War Veterans, the high rates of these conditions also found in Veterans who did not serve in the Gulf indicates a significant burden of disease in the population of this cohort of Veterans as a whole.
The investigators' findings suggest that military service, not solely deployment, has long-term health consequences.
Inflammation—In 2016, researchers at the VA Minneapolis Health Care System and the University of Minnesota reported they had developed a tentative panel of blood markers that can verify a diagnosis of CMI with 90 percent accuracy.
Their study found that several commonly used blood tests that indicate inflammation tended to yield different results when given to Veterans who reported symptoms consistent with CMI, and to those who did not. (Inflammation is the body's response to injury or infection.) The researchers believe that chronic inflammation in the body may be the chief underlying culprit of CMI.
Participants in the study included 85 Gulf War Veterans. The volunteers' blood samples were tested for red, white, and platelet counts, and for more than 60 different proteins. Those with significantly higher levels of lymphocytes, monocytes, and C reactive protein could be correctly diagnosed with CMI 90 percent of the time, when their probability of having the illness was greater than 70 percent.
The results now need to be validated in larger groups of patients. However, the team is already working on a clinical trial to test whether an existing anti-inflammatory drug will improve health-related quality of life in Veterans with CMI.
Human leucocyte antigen—Human leukocyte antigen (HLA) is a protein found in most cells in the body. The protein regulates the immune system in humans.
In 2015, a research team from the Minneapolis VA Health Care System and the University of Minnesota found that the composition of HLA in Veterans with CMI was different from those without the illness. The researchers concluded that Veterans with CMI had reduced levels of protection from HLA, and were therefore more susceptible to the illness.
Reduced gray matter—In 2014, a research team at the San Francisco VA Health Care System and the University of California learned that Veterans whose sleep quality was poor had reduced gray matter volume in their brains. Gray matter is made up of neurons, the most important type of brain cell. White matter, by contrast, is made up of axons (long thin fibers that extend from neurons and relay messages).
The researchers studied 144 Gulf War Veterans, using a questionnaire asking them how long they sleep, how easily they fall asleep, how often they wake up during the night, and whether they find it hard to stay awake during the day.
Veterans who reported the worst sleep had the lowest total cortical and frontal gray matter volume, even after adjusting for age, PTSD, depression, CMI, past traumas, and the use of certain psychiatric drugs. According to the research team, the study does not necessarily prove that poor sleep causes reduced volume, and it is also unclear what impact treating poor sleep might have on the brain.
Chemical alarms and gray matter volume—In 2016, another San Francisco VA research team found that the higher the number of chemical alarms Veterans heard during their time in the Gulf, as per their self-reports, the lower their gray matter volume was, even after accounting for their current health status and other variables. The researchers concluded that exposure to the substances that triggered the alarms likely had adverse effects on the anatomy of the Veterans' brains.
Exposure to sarin and cyclosarin—VA researchers in San Francisco have also used magnetic resonance imaging to identify brain differences between Veterans who were exposed to the chemical warfare agents sarin and cyclosarin and those who were not exposed.
An imaging study completed in 2011 identified brain differences between the two groups. The findings "confirmed previous reports...of central nervous system pathology in Gulf War Veterans with suspected exposure to low levels of [sarin and cyclosarin] two decades after exposure."
A 2014 follow-up study at the site added evidence of differences in the hippocampus—an area of the brain crucial for learning and memory—in those Gulf War Veterans with suspected exposure, and a 2015 study found that exposure to sarin and cyclosarin may result in a "reorganization" of the brain's white matter, resulting in possible behaviorial changes.
The United States military uses depleted uranium (DU) in tank armor and in some bullets designed to penetrate enemy armored vehicles. It began using DU on a large scale during the Gulf War.
The process of manufacturing enriched uranium from the natural uranium used in nuclear reactors or weapons leaves "depleted" uranium. DU has 40 percent less radioactivity, but the same chemical toxicity, as natural uranium.
Fragments from armor-piercing rounds can subsequently hit troops and become embedded in their bodies. The metal is suspected as being one of the causes of CMI.
In 2011, researchers with the Baltimore VA Medical Center and the University of Maryland clinically evaluated 35 Veterans known to have been exposed to depleted uranium during the Gulf War.
They found that, although some Veterans still had higher-than-normal levels of uranium in their urine, there had been no significant evidence of clinically important changes to their bones and kidneys, the two areas uranium would most likely target. The investigators recommended continued surveillance of this issue.
Regenerating brain cells—In a 2013 study using rats at the Durham VA Medical Center and Duke University, researchers showed that exposure to chemicals linked to CMI caused mood and memory problems. These chemicals included pyridostigmine bromide, permethrin, and DEET.
Adding mild stress on the animals worsened the problems. The researchers pinpointed the specific changes in the brain that appeared to be responsible for the functional decline, such as reduced volume and increased inflammation in the hippocampus, and the loss of specific populations of neurons.
The study suggests that treatment strategies focused on brain cell regeneration and inflammation reduction may help Gulf War Veterans.
Light therapy—Researchers at the VA Boston Healthcare System are testing an innovative therapy for CMI that has shown promise in pilot work.
The therapy involves the application of red and near-infrared light to the scalp. Some Veterans in the study will 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. Others will get a sham version of the treatment.
The light is painless and generates no heat, and has been used successfully for wound healing and to treat muscle aches and pains, as well as joint problems.
The study will involve 160 Gulf War Veterans. Follow-up testing will measure changes in attention, learning, memory, and executive function, as well as pain, fatigue, and mood.
Exercise training—Researchers at the William S. Middleton VA Medical Center in Madison, Wisconsin, are studying the effects of 16 weeks of resistance exercise training on chronic muscle pain, such as that experienced by many Veterans with CMI.
More than 60 Gulf War Veterans are taking part. The study will track how exercise changes the brain's response to pain by using brain scans.
New brain-cell survival therapy—A VA and Boston University team is testing an experimental drug called 7,8-DHF, which is capable of crossing the blood-brain barrier and is reported to boost brain-cell survival.
The group is testing the drug in a mouse model of CMI that reflects exposure to toxins and stress. The researchers believe the new drug, combined with moderate exercise, may represent a new therapy approach to help Gulf War Veterans.
Exploring gender differences—Women with CMI have been an understudied group, according to researchers at the Miami VA Health Care System.
A research team is conducting detailed biomedical studies on Gulf War Veterans of both genders, based on blood samples, to understand key differences that may lead to tailored diagnosis and therapy for women.
The work complements previous studies group on women with chronic fatigue syndrome or fibromyalgia. It is scheduled to be conducted in 2018.
Multiple sclerosis not related to deployment—In 2014, a VA team compared the clinical and military histories of nearly 700,000 deployed and 1.8 million nondeployed personnel from the Gulf War era to look for trends in multiple sclerosis and other diseases that cause deterioration of the myelin sheath that insulates nerves and allows them to function.
The study found no correlation between Gulf War deployment and multiple sclerosis risk.
Genetic study and biorepository—VA is undertaking a genetic study of Gulf War Veterans that will include collecting survey data and banking blood in a biorepository to better understand genetic influences on CMI and how Veterans respond to treatment.
Study participants must agree to donate their brain and other body tissues at the time of their death, but they are followed over their life span.
Researchers say the medical, lifestyle, and exposure data they collect will provide valuable clues to the health challenges faced by Veterans of the Gulf War and other conflicts.
Illnesses among United States Veterans of the Gulf War: a population-based survey of 30,000 Veterans. Kang HK, Mahan CM, Lee KY, Magee CA, Murphy FM. In comparison with their peers, Gulf Veterans had a higher prevalence of functional impairment, health care utilization, symptoms, and medical conditions, and a higher rate of low general health perceptions. J Occup Environ Med. 2000 May;42(5):491-501.
Cognitive behavioral therapy and aerobic exercise for Gulf War Veterans' illnesses: a randomized controlled trial. Donta ST et al. Cognitive behavioral therapy and exercise, separately and together, can provide modest relief for some of the symptoms of CMI. JAMA, 2003 Mar 19;288(11)
Occurrence of amyotrophic lateral sclerosis among Gulf War Veterans. Horner RD, Kamins KG, Feussner JR, Grambow SC, Hoff-Lindquist J, Harati Y, Mitsumoto H, Pascuzzi R, Spencer PS, Tim R, Howard D, Smith TC, Ryan MA, Coffman CJ, Kasarskis EJ. Military personnel who were deployed to the Gulf region during the Gulf War period experienced a greater postwar risk of ALS than those who were not deployed to the Gulf. Neurology, 2003 Sep 23;61(6);742-9
Effects of low-level exposure to sarin and cyclosarin during the 1991 Gulf War on brain function and brain structure in US Veterans. Chao LL, Rothlind JC, Cardenas, VA, Meyerhoff DJ, Weiner MW. Low-level exposure to the chemical warfare agents sarin and cyclosarin can have deleterious effects on brain structure and brain function more than a decade later. Neurotoxicology, 2010 September; 31(5);493-501
Measures of genotoxicity in Gulf War I Veterans exposed to depleted uranium. McDiarmid MA, Albertini RJ, Tucker JD, Vacek PM, Carter EW, Bakhmutsky MV, Oliver MS, Engelhardt SM, Squibb KS. A comprehensive evaluation of a human population chronically exposed to depleted uranium demonstrating a relatively weak genotoxic effect of the exposure. Environ Mol Mutagen. 2011 Aug;52(7);52(7):569-81.
Inspiratory airflow dynamics during sleep in Veterans with Gulf War Illness: a controlled study. Amin MM, Belisova Z, Hossain S, Gold MS, Broderick JE, Gold AR. Veterans with CMI experience sleep-disordered breathing that may distinguish them from asymptomatic Veterans of the war. Sleep Breath, 2011 Sep;15(3):333-9.
Longitudinal Health study of US 1991 Gulf War Veterans: changes in health status at 10-year follow up. Li B, Mahan CM, Hang HK, Eisen SA, Engel SA. During the 10-year period from 1995 to 2005, the health of deployed Veterans worsened in comparison with that of non-deployed Veterans because of a higher rate of new onset of various health outcomes and greater persistence of previously reported adverse health conditions. Am J Epidemiol, 2011 Oct 1;174(7);761-8
Multiple sclerosis in Gulf War era veterans. 2. Military deployment and risk of multiple sclerosis in the first Gulf War. Wallin Mt, Kurtzke JF, Culpepper WJ, Coffman P, Maloni H, Haselkorn JK, Mahan CM. Military deployment to the first Gulf War was not a risk factor for developing multiple sclerosis. Neuroepidemiology. 2014;42(4):226-34.
Effects of low-level sarin and cyclosarin exposure on with matter integrity in Gulf War Veterans. Chao LL, Zhang Y, Buckley S. It is possible that widespread increases in axial diffusivity observed in Gulf War Veterans who may have been exposed to sarin or cyclosarin may reflect white-matter reorganization after their exposure. Neurotoxicology. 2015 May;48:239-48,
Using gene expression signatures to identify novel treatment strategies in Gulf War illness. Craddock TJ, Harvey JM, Nathanson L, Barnes ZM, Klimas NG, Fletcher MA, Broderick G. Immunosuppressants currently used in treating rheumatoid arthritis and hormone-based therapies were identified as the best available candidates for treating CMI symptoms. BMC Med Genomics. 2015 Jul 9;8:36.
Reduced human leukocyte antigen protection in Gulf War Illness. Georgopoulos AP, James LM, Mahan MY, Joseph J, Georgopoulos A, Engdahl BE. There is a reduced HLA protection in Veterans with CMI. EBioMedicine. 2015 Nov 22;3:79-85.
Physical and mental health status of Gulf War and Gulf Era Veterans: results from a large population-based epidemiological study. Dursa EK, Barth SK, Schneiderman AI, Bossarte RM. Gulf War Veterans continue to report poorer heath than Gulf-era Veterans, based on data collected some 20 years after the war. Chronic disease management and interventions to improve health and wellness among both Gulf War and Gulf-erara Veterans are necessary. J Occup Environ Med. 2016 Jan;58(1):41-6.
A randomized, double-blind, placebo-controlled, crossover trial of mifepristone in Gulf War Veterans with chronic multisymptom illness. A moderate dose of mifepristone may have cognitive-enhancing effects in CMI. Psychoneuroendocrinology. 2016 Feb;64:22-30.
Associations between the self-reported frequency of hearing chemical alarms in theater and regional brain volume in Gulf War Veterans. Chao LL, Reeb R, Esparza IL, Abadjian LR. There is an inverse association between the self-reported frequency of hearing chemical alarms sound during the Gulf War and total cortical gray matter. Neurotoxicology. 2016 Mar;53:246-56.
Blood biomarkers of chronic inflammation in Gulf War illness. Johnson GJ, Slater BC, Leis LA, Rector TS, Bach RR. Inflammation is a component of the pathobiology of Gulf War Illness. Analysis of the data resulted in a model utilizing three readily measurable biomarkers. PLoS One. 2016 Jun 28;11(6):e0157855.