A review of medical studies on Gulf War syndrome supports the theory that the still-hazy disorder was caused by a group of related chemicals found in pesticides used around military facilities and anti-nerve-gas pills given to soldiers, according to a study released Monday.
A similar chemical was also found in nerve gas that was inadvertently released when U.S. soldiers destroyed a munitions depot just after the 1991 war, according to the study published in the Proceedings of the National Academy of Sciences.
The group of chemicals, known as acetylcholinesterase inhibitors, has long been discussed as a possible cause of Gulf War syndrome.
The review "thoroughly, conclusively shows that this class of chemicals actually are a cause of illness in Gulf War veterans," said Dr. Beatrice Golomb, an associate professor of medicine at UC San Diego and the author of the latest paper.
Other researchers, however, said the syndrome's symptoms are so varied that it's probably difficult to place the blame on a single cause.
"It seems clear at this point, 17 years beyond the conflict, that the chances we will ever resolve this with any single 'smoking gun' exposure grows smaller with time," said Dr. Charles Engel, director of the Department of Defense Deployment Health Clinical Center at Walter Reed Army Medical Center in Washington.
Gulf War syndrome is a complex -- and controversial -- illness typically characterized by a variety of symptoms, including fatigue, muscle or joint pain and mood problems. About 200,000 veterans are believed to suffer from it, according to the study.
But there is still uncertainty. A panel of the federal Institute of Medicine said in 2006 that it could not say if there was a coherent set of symptoms that pointed to an identifiable syndrome.
Researchers have proposed a number of potential causes, including psychological stress and exposure to toxic materials from oil-well fires and depleted-uranium ammunition, experts said.
In toxic doses, acetylcholinesterase inhibitors cause unbridled signaling between cells, potentially leading to muscle paralysis, seizures and excess secretion in the airways.
Previous studies have estimated that at least 250,000 soldiers were exposed to some form of the chemical.
Golomb's study looked at more than 70 studies on Gulf War syndrome and acetylcholinesterase inhibitors.
She found that 18 of the 21 epidemiological studies looking at chronic health problems in Gulf War veterans showed a connection to at least one kind of acetylcholinesterase inhibitor exposure.
Golomb also noted several studies that found sick veterans were more likely to have an enzyme problem that lowered their ability to clear the chemicals from their bodies.
Several studies also found Gulf War syndrome-like symptoms in farmworkers exposed to pesticides and victims of the 1995 sarin gas attacks in Japan. Some of the studies showed similar enzyme deficiencies.
The analysis found few studies that confirmed connections to other causes for Gulf War syndrome.
"The importance of this paper is that it brings together research from different realms, which are all parallel and point in the same direction," said Lea Steele, an epidemiologist who has served as scientific advisor to the Department of Veterans Affairs. She was not involved in the analysis.
Engel, of Walter Reed, said he was unconvinced -- in part because there is little, if any, accurate measurement of chemical exposures during the war.
"It is well known that significant error results from looking back years after the fact and asking people to try to recall potential exposures," he said.